Lee H

References (46)

Title : Designer molecules of the synaptic organizer MDGA1 reveal 3D conformational control of biological function - Lee_2023_J.Biol.Chem__104586
Author(s) : Lee H , Chofflet N , Liu J , Fan S , Lu Z , Rojas M , Penndorf P , Bailey A , Russell W , Machius M , Ren G , Takahashi H , Rudenko G
Ref : Journal of Biological Chemistry , :104586 , 2023
Abstract : MDGAs (MAM domain-containing glycosylphosphatidylinositol anchors) are synaptic cell surface molecules that regulate the formation of trans-synaptic bridges between neurexins (NRXNs) and neuroligins (NLGNs) which promote synaptic development. Mutations in MDGAs are implicated in various neuropsychiatric diseases. MDGAs bind NLGNs in cis on the postsynaptic membrane and physically block NLGNs from binding to NRXNs. In crystal structures, the six immunoglobulin (Ig) and single fibronectin III (FN3) domains of MDGA1 reveal a striking compact, triangular shape, both alone and in complex with NLGNs. Whether this unusual domain arrangement is required for biological function or other arrangements occur with different functional outcomes is unknown. Here, we show that wild-type MDGA1 can adopt both compact and extended 3D conformations that bind NLGN2. Designer mutants targeting strategic molecular elbows in MDGA1 alter the distribution of 3D conformations while leaving the binding affinity between soluble ectodomains of MDGA1 and NLGN2 intact. In contrast, in a cellular context, these mutants result in unique combinations of functional consequences, including altered binding to NLGN2, decreased capacity to conceal NLGN2 from NRXN1beta, and/or suppressed NLGN2-mediated inhibitory presynaptic differentiation, despite the mutations being located far from the MDGA1:NLGN2 interaction site. Thus, the 3D conformation of the entire MDGA1 ectodomain appears critical for its function, and its NLGN-binding site on Ig1-Ig2 is not independent of the rest of the molecule. As a result, global 3D conformational changes to the MDGA1 ectodomain via strategic elbows may form a molecular mechanism to regulate MDGA1 action within the synaptic cleft.
ESTHER : Lee_2023_J.Biol.Chem__104586
PubMedSearch : Lee_2023_J.Biol.Chem__104586
PubMedID: 36889589

Title : Physiological roles and regulation of hepatic angiopoietin-like protein 3 in Japanese Black cattle (Bos taurus) during the fattening period - Shikida_2023_J.Anim.Sci__
Author(s) : Shikida R , Kim M , Futohashi M , Nishihara K , Lee H , Suzuki Y , Baek Y , Masaki T , Ikuta K , Iwamoto E , Uemoto Y , Haga S , Terada F , Roh S
Ref : J Anim Sci , : , 2023
Abstract : Angiopoietin-like protein 3 (ANGPTL3) is expressed predominantly in the liver and plays a major role in regulating the circulating triglyceride and lipoprotein fraction concentrations by inhibiting lipoprotein lipase (LPL) activity. Given these physiological roles, ANGPTL3 may play an important role in metabolic changes related to fat accumulation during the fattening period in Japanese Black. This study aimed to reveal the physiological roles of hepatic ANGPTL3 in Japanese Black steers (Bos taurus) during the fattening period and investigate the regulatory effects of hepatic ANGPTL3. To investigate the gene expression and protein localization of ANGPTL3, 18 tissue samples were collected from tree male Holstein bull calves aged 7 weeks. Biopsied liver tissues and blood samples were collected from 21 Japanese Black steers during the early (T1; 13 months of age), middle (T2; 20 months), and late fattening phases (T3; 28 months). Relative mRNA expression, blood metabolite concentrations, hormone concentrations, growth, and carcass traits were analyzed. To identify the regulatory factors of hepatic ANGPTL3, primary bovine hepatocytes collected by 2 Holstein calves aged 7 weeks were incubated with insulin, palmitate, oleate, propionate, acetate, or beta-hydroxybutyric acid (BHBA). The ANGPTL3 gene was most highly expressed in the liver, with minor expression in the renal cortex, lungs, reticulum, and jejunum in Holstein bull calves. In Japanese Black steers, relative ANGPTL3 mRNA expressions were less as fattening progressed, and blood triglyceride, total cholesterol, and non-esterified fatty acid (NEFA) concentrations increased. Relative ANGPTL8 and Liver X receptor alpha (LXRalpha) mRNA expressions decreased in late and middle fattening phases, respectively. Furthermore, relative ANGTPL3 mRNA expression was positively correlated with ANGPTL8 (r = 0.650; P < 0.01) and ANGPTL4 (r = 0.540; P < 0.05) in T3 and T1, respectively, and LXRalpha showed no correlation with ANGPTL3. Relative ANGTPL3 mRNA expression was negatively correlated with total cholesterol (r = -0.434; P < 0.05) and triglyceride (r = -0.645; P < 0.01) concentrations in T3 and T1, respectively; There was no significant correlation between ANGTPL3 and carcass traits. Relative ANGTPL3 mRNA expression in cultured bovine hepatocytes was downregulated in oleate treatment. Together, these findings suggest that ANGPTL3 downregulation in late fattening phases is associated with the changes in lipid metabolism.
ESTHER : Shikida_2023_J.Anim.Sci__
PubMedSearch : Shikida_2023_J.Anim.Sci__
PubMedID: 37317898

Title : Heterologous expression, purification, and characterization of a recombinant Cordyceps militaris lipase from Candida rugosa-like family in Pichia pastoris - Lee_2023_Enzyme.Microb.Technol_168_110254
Author(s) : Lee J , Lee H , Chang PS
Ref : Enzyme Microb Technol , 168 :110254 , 2023
Abstract : Multiple sequence alignments of three lipase isoforms from the filamentous fungus, Cordyceps militaris, have revealed that the deduced protein from their common sequence belongs to the Candida rugosa lipase-like group. To express the protein in its active form, recombinant lipase from C. militaris (rCML) was extra cellularly expressed in Pichia pastoris X-33 after removing its signal peptide. Purified rCML was a stable monomeric protein with a molecular mass of 90 kDa, and was highly N-mannosylated compared to the native protein (69 kDa). The catalytic efficiency (k(cat)/K(m)) of rCML was greater than the native protein (1244.35 +/- 50.88 and 1067.17 +/- 29.07 mM(-1).min(-1), respectively), yet they had similar optimal pH values and temperatures (40 degreesC and pH 7.0-7.5), and showed preferences for Tween esters and short-chain triacylglycerols. Despite its monomeric conformation, interfacial activation was not observed for rCML, unlike the classical lipases. From the structural model of rCML, the binding pocket of rCML was predicted as a funnel-like structure consisting of a hollow space and an intramolecular tunnel, which is typical of C. rugosa lipase-like lipases. However, a blockage shortened the tunnel to 12-15 A, which endows strict short-chain selectivity towards triacylglycerols and a perfect match for tricaproin (C6:0). The limited depth of the tunnel may enable accommodation of triacylglycerols with medium-to-long-chain fatty acids, which differentiates rCML from other C. rugosa lipase-like lipases with broad substrate specificities.
ESTHER : Lee_2023_Enzyme.Microb.Technol_168_110254
PubMedSearch : Lee_2023_Enzyme.Microb.Technol_168_110254
PubMedID: 37201411
Gene_locus related to this paper: cormm-g3j8e9

Title : Tsaokoic Acid: A New Bicyclic Nonene from the Fruits of Amomum tsao-ko with Acetylcholinesterase Inhibitory Activity - Kim_2023_Molecules_28_
Author(s) : Kim H , Lee H , Jung HJ , Noh SG , Youn I , Kwak H , Lee Y , Nam SJ , Kang S , Chung HY , Seo EK
Ref : Molecules , 28 : , 2023
Abstract : A new bicyclic nonene, tsaokoic acid (1), was isolated from the fruits of Amomum tsao-ko, together with three known compounds (2-4). The structure of 1 was elucidated by analyzing spectroscopic data including 1D and 2D NMR spectra and compounds 2-4 were identified as tsaokoin, vanillin, and tsaokoarylone, respectively, by comparing their NMR spectra with previously reported data. Compounds 1-4 showed possible inhibitory activity against acetylcholinesterase (AChE) in silico molecular docking simulations. They were submitted to in vitro assay system and exhibited moderate inhibitory activity with IC(50) values of 32.78, 41.70, 39.25, and 31.13 microM, respectively.
ESTHER : Kim_2023_Molecules_28_
PubMedSearch : Kim_2023_Molecules_28_
PubMedID: 36985573

Title : Donepezil ameliorates Abeta pathology but not tau pathology in 5xFAD mice - Choi_2022_Mol.Brain_15_63
Author(s) : Choi HJ , Park JH , Jeong YJ , Hwang JW , Lee S , Lee H , Seol E , Kim IW , Cha BY , Seo J , Moon M , Hoe HS
Ref : Mol Brain , 15 :63 , 2022
Abstract : The cholinesterase inhibitor donepezil is used to improve Abeta pathology and cognitive function in patients with Alzheimer's disease (AD). However, the impact of donepezil on tau pathology is unclear. Thus, we examined the effects of donepezil on Abeta and tau pathology in 5xFAD mice (a model of AD) in this study. We found that intraperitoneal injection of donepezil (1 mg/kg, i.p.) exhibited significant reductions in Abeta plaque number in the cortex and hippocampal DG region. In addition, donepezil treatment (1 mg/kg, i.p.) reduced Abeta-mediated microglial and, to a lesser extent, astrocytic activation in 5xFAD mice. However, neither intraperitoneal/oral injection of donepezil nor oral injection of rivastigmine altered tau phosphorylation at Thr212/Ser214 (AT100), Thr396, and Thr231 in 5xFAD mice. Surprisingly, we observed that intraperitoneal/oral injection of donepezil treatment significantly increased tau phosphorylation at Thr212 in 5xFAD mice. Taken together, these data suggest that intraperitoneal injection of donepezil suppresses Abeta pathology but not tau pathology in 5xFAD mice.
ESTHER : Choi_2022_Mol.Brain_15_63
PubMedSearch : Choi_2022_Mol.Brain_15_63
PubMedID: 35850693

Title : A chemical tool for blue light-inducible proximity photo-crosslinking in live cells - Mishra_2022_Chem.Sci_13_955
Author(s) : Mishra PK , Kang MG , Lee H , Kim S , Choi S , Sharma N , Park CM , Ko J , Lee C , Seo JK , Rhee HW
Ref : Chem Sci , 13 :955 , 2022
Abstract : We developed a proximity photo-crosslinking method (Spotlight) with a 4-azido-N-ethyl-1,8-naphthalimide (AzNP) moiety that can be converted to reactive aryl nitrene species using ambient blue light-emitting diode light. Using an AzNP-conjugated HaloTag ligand (VL1), blue light-induced photo-crosslinked products of various HaloTag-conjugated proteins of interest were detected in subcellular spaces in live cells. Chemical or heat stress-induced dynamic changes in the proteome were also detected, and photo-crosslinking in the mouse brain tissue was enabled. Using Spotlight, we further identified the host interactome of SARS-CoV-2 nucleocapsid (N) protein, which is essential for viral genome assembly. Mass analysis of the VL1-crosslinked product of N-HaloTag in HEK293T cells showed that RNA-binding proteins in stress granules were exclusively enriched in the cross-linked samples. These results tell that our method can reveal the interactome of protein of interest within a short distance in live cells.
ESTHER : Mishra_2022_Chem.Sci_13_955
PubMedSearch : Mishra_2022_Chem.Sci_13_955
Gene_locus related to this paper: rhoso-halo1

Title : Bioinformatic Expansion of Borosins Uncovers Trans-Acting Peptide Backbone N-Methyltransferases in Bacteria - Cho_2022_Biochemistry_61_183
Author(s) : Cho H , Lee H , Hong K , Chung H , Song I , Lee JS , Kim S
Ref : Biochemistry , 61 :183 , 2022
Abstract : Backbone N-methylation is one of the prominent peptide modifications that can greatly enhance the pharmacological properties of a peptide. Naturally occurring backbone N-methylated peptides are produced via nonribosomal or ribosomal pathways, the latter of which was only recently identified in the borosin family of ribosomally synthesized and post-translationally modified peptides. Although previous bioinformatic analyses have revealed new putative genes for borosin biosynthesis, the natural scope of structural and biosynthetic diversity of the borosin family has not been thoroughly explored. Here, we report a comprehensive overview of the borosin family of peptide natural products. Using a genome mining approach, we identified more than 1400 new putative biosynthetic gene clusters for borosins and demonstrated that, unlike those previously reported, most of them are found in bacterial genomes and encode a precursor peptide unfused to its cognate methyltransferase enzyme. Biochemical analysis confirmed the backbone N-methylation of the precursor peptide in trans in eight enzyme-precursor pairs and revealed two novel types of enzyme-recognizing sequences in the precursor peptide. This work significantly expands the biosynthetic diversity of borosins and paves the way for the enzymatic production of diverse backbone N-methylated peptides.
ESTHER : Cho_2022_Biochemistry_61_183
PubMedSearch : Cho_2022_Biochemistry_61_183
PubMedID: 35061348

Title : Assessments of the In Vitro and In Vivo Linker Stability and Catabolic Fate for the Ortho Hydroxy-Protected Aryl Sulfate Linker by Immuno-Affinity Capture Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometric Assay - Lee_2021_Pharmaceutics_13_
Author(s) : Lee BI , Park SJ , Park Y , Shin SH , Choi JM , Park MJ , Lim JH , Kim SY , Lee H , Shin YG
Ref : Pharmaceutics , 13 : , 2021
Abstract : Antibody-drug conjugate (ADC) linkers play an important role in determining the safety and efficacy of ADC. The Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linker is a newly developed linker in the form of a di-aryl sulfate structure consisting of phenolic payload and self-immolative group (SIG). In this study, using two bioanalytical approaches (namely "bottom-up" and "middle-up" approaches) via the liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method, in vitro and in vivo linker stability experiments were conducted for the OHPAS linker. For comparison, the valine-citrulline-p-aminobenzyloxycarbonyl (VC-PABC) linker was also evaluated under the same experimental conditions. In addition, the catabolite identification experiments at the subunit intact protein level were simultaneously performed to evaluate the catabolic fate of ADCs. As a result, the OHPAS linker was stable in the in vitro mouse/human plasma as well as in vivo pharmacokinetic studies in mice, whereas the VC-PABC linker was relatively unstable in mice in vitro and in vivo. This is because the VC-PABC linker was sensitive to a hydrolytic enzyme called carboxylesterase 1c (Ces1c) in mouse plasma. In conclusion, the OHPAS linker appears to be a good linker for ADC, and further experiments would be warranted to demonstrate the efficacy and toxicity related to the OHPAS linker.
ESTHER : Lee_2021_Pharmaceutics_13_
PubMedSearch : Lee_2021_Pharmaceutics_13_
PubMedID: 33478046
Gene_locus related to this paper: mouse-Ces1c

Title : CRISPR-Knockout of CSE Gene Improves Saccharification Efficiency by Reducing Lignin Content in Hybrid Poplar - Jang_2021_Int.J.Mol.Sci_22_
Author(s) : Jang HA , Bae EK , Kim MH , Park SJ , Choi NY , Pyo SW , Lee C , Jeong HY , Lee H , Choi YI , Ko JH
Ref : Int J Mol Sci , 22 : , 2021
Abstract : Caffeoyl shikimate esterase (CSE) has been shown to play an important role in lignin biosynthesis in plants and is, therefore, a promising target for generating improved lignocellulosic biomass crops for sustainable biofuel production. Populus spp. has two CSE genes (CSE1 and CSE2) and, thus, the hybrid poplar (Populus alba x P. glandulosa) investigated in this study has four CSE genes. Here, we present transgenic hybrid poplars with knockouts of each CSE gene achieved by CRISPR/Cas9. To knockout the CSE genes of the hybrid poplar, we designed three single guide RNAs (sg1-sg3), and produced three different transgenic poplars with either CSE1 (CSE1-sg2), CSE2 (CSE2-sg3), or both genes (CSE1/2-sg1) mutated. CSE1-sg2 and CSE2-sg3 poplars showed up to 29.1% reduction in lignin deposition with irregularly shaped xylem vessels. However, CSE1-sg2 and CSE2-sg3 poplars were morphologically indistinguishable from WT and showed no significant differences in growth in a long-term living modified organism (LMO) field-test covering four seasons. Gene expression analysis revealed that many lignin biosynthetic genes were downregulated in CSE1-sg2 and CSE2-sg3 poplars. Indeed, the CSE1-sg2 and CSE2-sg3 poplars had up to 25% higher saccharification efficiency than the WT control. Our results demonstrate that precise editing of CSE by CRISPR/Cas9 technology can improve lignocellulosic biomass without a growth penalty.
ESTHER : Jang_2021_Int.J.Mol.Sci_22_
PubMedSearch : Jang_2021_Int.J.Mol.Sci_22_
PubMedID: 34575913
Gene_locus related to this paper: arath-F14G24.3

Title : Genetic Evaluation of Congenital Hypothyroidism with Gland in situ Using Targeted Exome Sequencing - Shin_2021_Ann.Clin.Lab.Sci_51_73
Author(s) : Shin JH , Kim HY , Kim YM , Lee H , Bae MH , Park KH , Lee SM , Kwak MJ
Ref : Annals of Clinical & Laboratory Science , 51 :73 , 2021
Abstract : OBJECTIVE: To analyze the genetic causes of congenital hypothyroidism through the targeted exome sequencing of pediatric patients with congenital hypothyroidism with thyroid gland in situ. METHOD: The study population included 20 patients diagnosed with congenital hypothyroidism with thyroid gland in situ at the Pediatric Endocrinology Clinic of Pusan National University Hospital. Targeted exome sequencing was performed on eight causative genes, including thyroid stimulating hormone receptor (TSHR), mutation in which can cause hypothyroidism with a small or normal sized thyroid gland, and thyroglobulin (TG), thyroid peroxidase (TPO), dual oxidase 2 (DUOX2), dual oxidase maturation factor 2 (DUOXA2), iodotyrosine deiodinase (IYD), solute carrier family 26 member 4 (SLC26A4), and solute carrier family 5 member 5 (SLC5A5), mutations in which are known to cause thyroid dyshormonogenesis. RESULTS: Permanent, subclinical, and transient hypothyroidism were diagnosed in 15 (75%), three (15%), and two (10%) patients, respectively. Genetic mutations were identified in 16 patients (80% positivity rate). Targeted exome sequencing of eight genes identified 24 variants in these patients: 11 DUOX2 variants in eight patients; six TSHR variants in five patients; five TG variants in three patients; and two DUOXA2 variants in two patients. Of these 24 variants, 10 (41.6%) were novel. No variants were identified in TPO, IYD, SLC5A5, or SLC26A4. Two patients displayed triallelic (digenic) mutations (in TG and TSHR in one patient and DUOX2 and TSHR in the other). No variants were identified in three patients with permanent hypothyroidism and one patient with transient hypothyroidism. Genetic variations that could explain the congenital hypothyroidism phenotypes were identified in 12/15 cases (80%). CONCLUSIONS: Targeted exome sequencing identified the genetic causes of congenital hypothyroidism with thyroid gland in situ in 80% of the patients studied, with DUOX2 and TSHR mutations being the most common. As many of the identified variants were novel, additional studies on the genetic causes of congenital hypothyroidism are warranted.
ESTHER : Shin_2021_Ann.Clin.Lab.Sci_51_73
PubMedSearch : Shin_2021_Ann.Clin.Lab.Sci_51_73
PubMedID: 33653783

Title : Donepezil Regulates LPS and Abeta-Stimulated Neuroinflammation through MAPK\/NLRP3 Inflammasome\/STAT3 Signaling - Kim_2021_Int.J.Mol.Sci_22_
Author(s) : Kim J , Lee HJ , Park SK , Park JH , Jeong HR , Lee S , Lee H , Seol E , Hoe HS
Ref : Int J Mol Sci , 22 : , 2021
Abstract : The acetylcholinesterase inhibitors donepezil and rivastigmine have been used as therapeutic drugs for Alzheimer's disease (AD), but their effects on LPS- and Abeta-induced neuroinflammatory responses and the underlying molecular pathways have not been studied in detail in vitro and in vivo. In the present study, we found that 10 or 50 microM donepezil significantly decreased the LPS-induced increases in the mRNA levels of a number of proinflammatory cytokines in BV2 microglial cells, whereas 50 microM rivastigmine significantly diminished only LPS-stimulated IL-6 mRNA levels. In subsequent experiments in primary astrocytes, donepezil suppressed only LPS-stimulated iNOS mRNA levels. To identify the molecular mechanisms by which donepezil regulates LPS-induced neuroinflammation, we examined whether donepezil alters LPS-stimulated proinflammatory responses by modulating LPS-induced downstream signaling and the NLRP3 inflammasome. Importantly, we found that donepezil suppressed LPS-induced AKT/MAPK signaling, the NLRP3 inflammasome, and transcription factor NF-kB/STAT3 phosphorylation to reduce neuroinflammatory responses. In LPS-treated wild-type mice, a model of neuroinflammatory disease, donepezil significantly attenuated LPS-induced microglial activation, microglial density/morphology, and proinflammatory cytokine COX-2 and IL-6 levels. In a mouse model of AD (5xFAD mice), donepezil significantly reduced Abeta-induced microglial and astrocytic activation, density, and morphology. Taken together, our findings indicate that donepezil significantly downregulates LPS- and Abeta-evoked neuroinflammatory responses in vitro and in vivo and may be a therapeutic agent for neuroinflammation-associated diseases such as AD.
ESTHER : Kim_2021_Int.J.Mol.Sci_22_
PubMedSearch : Kim_2021_Int.J.Mol.Sci_22_
PubMedID: 34638977

Title : A caffeic acid-ferulic acid hybrid compound attenuates lipopolysaccharide-mediated inflammation in BV2 and RAW264.7 cells - Kwon_2019_Biochem.Biophys.Res.Commun_515_565
Author(s) : Kwon MY , Kim SM , Park J , Lee J , Cho H , Lee H , Jeon C , Park JH , Han IO
Ref : Biochemical & Biophysical Research Communications , 515 :565 , 2019
Abstract : In the present study, we synthesized and evaluated the anti-inflammatory effects of the two component hybrids, caffeic acid (CA)-ferulic acid (FA), FA-Tryptamine (Trm), CA-Piperonyl Triazol (PT) and FA-PT. Of these five hybrids, CA-FA had the most potent inhibitory effect on butyrylcholinesterase (BuChE) activity. The CA containing hybrids, CA-FA, CA-Trm, and CA-PT, dose-dependently inhibited LPS-induced nitric oxide (NO) generation in BV2 cells, whereas FA-PT, FA-Trm, CA, FA, Trm, and PT did not. Although CA-FA, CA-Trm and CA-PT had similar inhibitory effects on LPS-induced NO generation, CA-FA best protected BV2 cells from LPS-induced cell death. CA-FA, but not CA or FA, dose-dependently inhibited LPS-induced up-regulations of NO synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions in BV2 and RAW264.7cells. Furthermore, CA-FA inhibited LPS-induced iNOS, COX-2, interleukin-6, and interleukin-1beta mRNA expressions in BV2 cells. CA-FA also inhibited the LPS-induced phosphorylations of STAT3, Akt, and IkappaB and selectively inhibited LPS-induced NF-kappaB activation. Overall, our data suggest that CA-FA has BuChE inhibitory effects and down-regulates inflammatory responses by inhibiting NF-kappaB, which indicates CA-FA be viewed as a potential therapeutic agent for the treatment of inflammatory diseases of the peripheral system and central nervous systems.
ESTHER : Kwon_2019_Biochem.Biophys.Res.Commun_515_565
PubMedSearch : Kwon_2019_Biochem.Biophys.Res.Commun_515_565
PubMedID: 31178135

Title : NOTUM Is Involved in the Progression of Colorectal Cancer - Yoon_2018_Cancer.Genomics.Proteomics_15_485
Author(s) : Yoon JH , Kim D , Kim J , Lee H , Ghim J , Kang BJ , Song P , Suh PG , Ryu SH , Lee TG
Ref : Cancer Genomics Proteomics , 15 :485 , 2018
Abstract : BACKGROUND: There are limitations to current colorectal cancer (CRC)-specific diagnostic methods and therapies. Tumorigenesis proceeds because of interaction between cancer cells and various surrounding cells; discovering new molecular mediators through studies of the CRC secretome is a promising approach for the development of CRC diagnostics and therapies. MATERIALS AND METHODS: A comparative secretomic analysis was performed using primary and metastatic human isogenic CRC cells. Proliferation was determined by MTT and thymidine incorporation assay, migration was determined by wound-healing assay (ELISA). The level of palmitoleoyl-protein carboxylesterase (NOTUM) in plasma from patients with CRC was determined by enzyme-linked immunosorbent assay. RESULTS: NOTUM expression was increased in metastatic cells. Proliferation was suppressed by inhibiting expression of NOTUM. Knockdown of NOTUM genes inhibited proliferation as well as migration, with possible involvement of p38 and c-JUN N-terminal kinase in this process. The result was verified in patients with CRC. CONCLUSION: NOTUM may be a new candidate for diagnostics and therapy of CRC.
ESTHER : Yoon_2018_Cancer.Genomics.Proteomics_15_485
PubMedSearch : Yoon_2018_Cancer.Genomics.Proteomics_15_485
PubMedID: 30343282

Title : Structure-guided synthesis of a protein-based fluorescent sensor for alkyl halides - Kang_2017_Chem.Commun.(Camb)_53_9226
Author(s) : Kang MG , Lee H , Kim BH , Dunbayev Y , Seo JK , Lee C , Rhee HW
Ref : Chem Commun (Camb) , 53 :9226 , 2017
Abstract : Alkyl halides are potentially mutagenic carcinogens. However, no efficient fluorescent sensor for alkyl halide detection in human-derived samples has been developed to date. Herein, we report a new protein-based fluorescent sensor for alkyl halides. Analysis of the HaloTag holo-crystal structure with its covalently attached ligand revealed an unexpected cavity, allowing for the design of a new fluorogenic ligand. This ligand showed the highest fluorescence response (300-fold) and fastest binding kinetics (t1/2 < 150 s) to a HaloTag mutant (M175P) protein. This protein-based sensor system was effectively used to detect alkyl halides in human serum and monitor real-time protein alkylation.
ESTHER : Kang_2017_Chem.Commun.(Camb)_53_9226
PubMedSearch : Kang_2017_Chem.Commun.(Camb)_53_9226
PubMedID: 28766590
Gene_locus related to this paper: rhoso-halo1

Title : The novel carboxylesterase 1 variant c.662A>G may decrease the bioactivation of oseltamivir in humans - Oh_2017_PLoS.One_12_e0176320
Author(s) : Oh J , Lee S , Lee H , Cho JY , Yoon SH , Jang IJ , Yu KS , Lim KS
Ref : PLoS ONE , 12 :e0176320 , 2017
Abstract : BACKGROUND: Human carboxylesterase 1 (CES1) is a serine esterase that hydrolyses various exogenous and endogenous compounds including oseltamivir, a prodrug used to treat influenza. A novel CES1 c.662A>G single nucleotide polymorphism (SNP) was predicted to decrease CES1 enzymatic activity in an in silico analysis. This study evaluated the effect of the c.662A>G SNP on the pharmacokinetics (PK) of oseltamivir in humans.
METHODS: A single oral dose of oseltamivir at 75 mg was administered to 20 healthy subjects, 8 heterozygous c.662A>G carriers (c.662AG) and 12 non-carriers (c.662AA). The concentrations of oseltamivir and its active metabolite, oseltamivir carboxylate, were measured in plasma and urine using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were calculated using a noncompartmental method. The geometric mean ratios (GMR, c.662AG to c.662AA) of the PK parameters and their 90% confidence intervals (CI) were calculated.
RESULTS: The systemic exposure to oseltamivir, as assessed by the AUC0-48h of oseltamivir, was increased by 10% in c.662AG subjects, whereas the AUC0-48h of oseltamivir carboxylate was 5% lower in c.662AG subjects. The GMR and 90% CI of the metabolic ratio (AUC0-48h, Oseltamivir carboxylate/AUC0-48h, Oseltamivir) was 0.87 (0.66-1.14). The amount of unchanged oseltamivir excreted in the urine was increased by 15% in subjects with the c.662AG genotype.
CONCLUSIONS: This result suggests that CES1 enzymatic activity may be decreased in these heterozygous allele carriers, although further studies are warranted to investigate the clinical implications of this genetic variation on CES1 substrate drugs. TRIAL REGISTRATION: ClinicalTtrials.gov NCT01902342.
ESTHER : Oh_2017_PLoS.One_12_e0176320
PubMedSearch : Oh_2017_PLoS.One_12_e0176320
PubMedID: 28437488

Title : Regulation of calcium release from the endoplasmic reticulum by the serine hydrolase ABHD2 - Yun_2017_Biochem.Biophys.Res.Commun_490_1226
Author(s) : Yun B , Lee H , Powell R , Reisdorph N , Ewing H , Gelb MH , Hsu KL , Cravatt BF , Leslie CC
Ref : Biochemical & Biophysical Research Communications , 490 :1226 , 2017
Abstract : The serine hydrolase inhibitors pyrrophenone and KT195 inhibit cell death induced by A23187 and H2O2 by blocking the release of calcium from the endoplasmic reticulum and mitochondrial calcium uptake. The effect of pyrrophenone and KT195 on these processes is not due to inhibition of their known targets, cytosolic phospholipase A2 and alpha/beta-hydrolase domain-containing (ABHD) 6, respectively, but represent off-target effects. To identify targets of KT195, fibroblasts were treated with KT195-alkyne to covalently label protein targets followed by click chemistry with biotin azide, enrichment on streptavidin beads and tryptic peptide analysis by mass spectrometry. Although several serine hydrolases were identified, alpha/beta-hydrolase domain-containing 2 (ABHD2) was the only target in which both KT195 and pyrrophenone competed for binding to KT195-alkyne. ABHD2 is a serine hydrolase with a predicted transmembrane domain consistent with its pull-down from the membrane proteome. Subcellular fractionation showed localization of ABHD2 to the endoplasmic reticulum but not to mitochondria or mitochondrial-associated membranes. Knockdown of ABHD2 with shRNA attenuated calcium release from the endoplasmic reticulum, mitochondrial calcium uptake and cell death in fibroblasts stimulated with A23187. The results describe a novel mechanism for regulating calcium transfer from the endoplasmic reticulum to mitochondria that involves the serine hydrolase ABHD2.
ESTHER : Yun_2017_Biochem.Biophys.Res.Commun_490_1226
PubMedSearch : Yun_2017_Biochem.Biophys.Res.Commun_490_1226
PubMedID: 28684316
Gene_locus related to this paper: human-ABHD2

Title : Soluble epoxide hydrolase inhibitory activity of components from Leonurus japonicus - Leem_2017_Int.J.Biol.Macromol_103_451
Author(s) : Leem HH , Lee GY , Lee JS , Lee H , Kim JH , Kim YH
Ref : Int J Biol Macromol , 103 :451 , 2017
Abstract : One new compound, 10-methoxy-leonurine (1), and four known compounds (2-5) were purified by silica gel, C-18, and Sephadex LH-20 column chromatography from Leonurus japonicus. Their structures were elucidated using one-dimensional (1D)/two-dimensional (2D)-nuclear magnetic resonance (NMR), high-resolution (HR)-electrospray ionization (ESI) mass spectrometry (MS). The compounds were evaluated to determine their inhibition of the catalysis of soluble epoxide hydrolase (sEH). According to the results from in vitro analyses, compounds 1 and 2, which contain guanidine and flavonoid (3), were determined to be potential inhibitors of this enzyme. All compounds were revealed to be non-competitive inhibitors according to Lineweaver-Burk plots. Furthermore, in silico molecular docking indicated that compounds 1-3 are bound to sEH in a similar fashion and have stable binding energies, as calculated by AutoDock 4.2. Molecular dynamics determined the root-mean-square deviation (RMSD), total energy, RMS fluctuation (RMSF), hydrogen bonds, and distance of the complex according to time.
ESTHER : Leem_2017_Int.J.Biol.Macromol_103_451
PubMedSearch : Leem_2017_Int.J.Biol.Macromol_103_451
PubMedID: 28501602

Title : Structural and Experimental Evidence for the Enantiomeric Recognition toward a Bulky sec-Alcohol by Candida antarctica Lipase B - Park_2016_ACS.Catal_6_7458
Author(s) : Park K , Kim S , Park J , Joe S , Min B , Oh J , Song J , Park SY , Park S , Lee H
Ref : , 6 :7458 , 2016
Abstract : Candida antarctica lipase B (CAL-B) exhibits remarkable enantioselectivity for various chiral sec-alcohols, and the enantioselectivity is structurally well-understood. Two substituents at the chiral center of a sec-alcohol separately bind two pockets, namely, large and medium binding pockets. It has been believed that the medium pocket is too small to accommodate a large substituent (larger than an ethyl group), and thus, bulky sec-alcohols bearing two large substituents have been regarded as a poor substrate for CAL-B. However, we found that CAL-B can catalyze the transesterification of N-Boc-protected rac-2-amino-1-phenylethanol (1a) enantioselectively with a moderate reaction rate. X-ray crystallography and computer modeling revealed that the rotation of the Leu278 side chain creates a space to accept the N-Boc-aminomethylene group of 1a. Moreover, a sec-alcohol substrate with less than one hydrogen atom at the gamma-position from the hydroxyl group is required to achieve a moderate reaction rate. On the basis of this observation, we diversified bulky N-Boc-protected rac-2-amino-1-arylethanols for the transesterifications with high enantioselectivities (E > 200).
ESTHER : Park_2016_ACS.Catal_6_7458
PubMedSearch : Park_2016_ACS.Catal_6_7458
Gene_locus related to this paper: canar-LipB

Title : Fermented Sipjeondaebo-tang Alleviates Memory Deficits and Loss of Hippocampal Neurogenesis in Scopolamine-induced Amnesia in Mice - Park_2016_Sci.Rep_6_22405
Author(s) : Park HR , Lee H , Park H , Cho WK , Ma JY
Ref : Sci Rep , 6 :22405 , 2016
Abstract : We investigated the anti-amnesic effects of SJ and fermented SJ (FSJ) on scopolamine (SCO)-induced amnesia mouse model. Mice were orally co-treated with SJ or FSJ (125, 250, and 500 mg/kg) and SCO (1 mg/kg), which was injected intraperitoneally for 14 days. SCO decreased the step-through latency and prolonged latency time to find the hidden platform in the passive avoidance test and Morris water maze test, respectively, and both SCO effects were ameliorated by FSJ treatment. FSJ was discovered to promote hippocampal neurogenesis during SCO treatment by increasing proliferation and survival of BrdU-positive cells, immature/mature neurons. In the hippocampus of SCO, oxidative stress and the activity of acetylcholinesterase were elevated, whereas the levels of acetylcholine and choline acetyltransferase were diminished; however, all of these alterations were attenuated by FSJ-treatment. The alterations in brain-derived neurotrophic factor, phosphorylated cAMP response element-binding protein, and phosphorylated Akt that occurred following SCO treatment were protected by FSJ administration. Therefore, our findings are the first to suggest that FSJ may be a promising therapeutic drug for the treatment of amnesia and aging-related or neurodegenerative disease-related memory impairment. Furthermore, the molecular mechanism by which FSJ exerts its effects may involve modulation of the cholinergic system and BDNF/CREB/Akt pathway.
ESTHER : Park_2016_Sci.Rep_6_22405
PubMedSearch : Park_2016_Sci.Rep_6_22405
PubMedID: 26939918

Title : The Combined Action of ENHANCED DISEASE SUSCEPTIBILITY1, PHYTOALEXIN DEFICIENT4, and SENESCENCE-ASSOCIATED101 Promotes Salicylic Acid-Mediated Defenses to Limit Fusarium graminearum Infection in Arabidopsis thaliana - Makandar_2015_Mol.Plant.Microbe.Interact_28_943
Author(s) : Makandar R , Nalam VJ , Chowdhury Z , Sarowar S , Klossner G , Lee H , Burdan D , Trick HN , Gobbato E , Parker JE , Shah J
Ref : Mol Plant Microbe Interact , 28 :943 , 2015
Abstract : Fusarium graminearum causes Fusarium head blight (FHB) disease in wheat and other cereals. F. graminearum also causes disease in Arabidopsis thaliana. In both Arabidopsis and wheat, F. graminearum infection is limited by salicylic acid (SA) signaling. Here, we show that, in Arabidopsis, the defense regulator EDS1 (ENHANCED DISEASE SUSCEPTIBILITY1) and its interacting partners, PAD4 (PHYTOALEXIN-DEFICIENT4) and SAG101 (SENESCENCE-ASSOCIATED GENE101), promote SA accumulation to curtail F. graminearum infection. Characterization of plants expressing the PAD4 noninteracting eds1(L262P) indicated that interaction between EDS1 and PAD4 is critical for limiting F. graminearum infection. A conserved serine in the predicted acyl hydrolase catalytic triad of PAD4, which is not required for defense against bacterial and oomycete pathogens, is necessary for limiting F. graminearum infection. These results suggest a molecular configuration of PAD4 in Arabidopsis defense against F. graminearum that is different from its defense contribution against other pathogens. We further show that constitutive expression of Arabidopsis PAD4 can enhance FHB resistance in Arabidopsis and wheat. Taken together with previous studies of wheat and Arabidopsis expressing salicylate hydroxylase or the SA-response regulator NPR1 (NON-EXPRESSER OF PR GENES1), our results show that exploring fundamental processes in a model plant provides important leads to manipulating crops for improved disease resistance.
ESTHER : Makandar_2015_Mol.Plant.Microbe.Interact_28_943
PubMedSearch : Makandar_2015_Mol.Plant.Microbe.Interact_28_943
PubMedID: 25915452

Title : Hydrogen-bonding-driven enantioselective resolution against the Kazlauskas rule to afford gamma-amino alcohols by Candida rugosa lipase - Min_2015_Chembiochem_16_77
Author(s) : Min B , Park J , Sim YK , Jung S , Kim SH , Song JK , Kim BT , Park SY , Yun J , Park S , Lee H
Ref : Chembiochem , 16 :77 , 2015
Abstract : Most lipases resolve secondary alcohols in accordance with the "Kazlauskas rule" to give the R enantiomers. In a similar manner to other lipases, Candida rugosa lipase (CRL) exhibits R enantioselectivity towards heptan-2-ol, although the enantiomeric ratio (E) is low (E=1.6). However, unexpected enantioselectivity (i.e., S enantioselectivity, E=58) of CRL towards 4-(tert-butoxycarbonylamino)butan-2-ol, which has a similar chain length to heptan-2-ol, has been observed. To develop a deeper understanding of the molecular basis for this unusual enantioselectivity, we have conducted a series of molecular modeling and substrate engineering experiments. The results of these computational and experimental analyses indicated that a hydrogen bond between the Ser450 residue and the nitrogen atom of the carbamate group is critical to stabilize the transition state of the S enantiomer.
ESTHER : Min_2015_Chembiochem_16_77
PubMedSearch : Min_2015_Chembiochem_16_77
PubMedID: 25477295
Gene_locus related to this paper: canru-1lipa

Title : Serine hydrolase inhibitors block necrotic cell death by preventing calcium overload of the mitochondria and permeability transition pore formation - Yun_2014_J.Biol.Chem_289_1491
Author(s) : Yun B , Lee H , Ghosh M , Cravatt BF , Hsu KL , Bonventre JV , Ewing H , Gelb MH , Leslie CC
Ref : Journal of Biological Chemistry , 289 :1491 , 2014
Abstract : Perturbation of calcium signaling that occurs during cell injury and disease, promotes cell death. In mouse lung fibroblasts A23187 triggered mitochondrial permeability transition pore (MPTP) formation, lactate dehydrogenase (LDH) release, and necrotic cell death that were blocked by cyclosporin A (CsA) and EGTA. LDH release temporally correlated with arachidonic acid release but did not involve cytosolic phospholipase A2alpha (cPLA2alpha) or calcium-independent PLA2. Surprisingly, release of arachidonic acid and LDH from cPLA2alpha-deficient fibroblasts was inhibited by the cPLA2alpha inhibitor pyrrophenone, and another serine hydrolase inhibitor KT195, by preventing mitochondrial calcium uptake. Inhibitors of calcium/calmodulin-dependent protein kinase II, a mitochondrial Ca(2+) uniporter (MCU) regulator, also prevented MPTP formation and arachidonic acid release induced by A23187 and H2O2. Pyrrophenone blocked MCU-mediated mitochondrial calcium uptake in permeabilized fibroblasts but not in isolated mitochondria. Unlike pyrrophenone, the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol and CsA blocked cell death and arachidonic acid release not by preventing mitochondrial calcium uptake but by inhibiting MPTP formation. In fibroblasts stimulated with thapsigargin, which induces MPTP formation by a direct effect on mitochondria, LDH and arachidonic acid release were blocked by CsA and 1-oleoyl-2-acetyl-sn-glycerol but not by pyrrophenone or EGTA. Therefore serine hydrolase inhibitors prevent necrotic cell death by blocking mitochondrial calcium uptake but not the enzyme releasing fatty acids that occurs by a novel pathway during MPTP formation. This work reveals the potential for development of small molecule cell-permeable serine hydrolase inhibitors that block MCU-mediated mitochondrial calcium overload, MPTP formation, and necrotic cell death.
ESTHER : Yun_2014_J.Biol.Chem_289_1491
PubMedSearch : Yun_2014_J.Biol.Chem_289_1491
PubMedID: 24297180

Title : Expression of a lipase on the cell-surface of Escherichia coli using the OmpW anchoring motif and its application to enantioselective reactions - Lee_2013_Biotechnol.Lett_35_1677
Author(s) : Lee H , Park SJ , Han MJ , Eom GT , Choi MJ , Kim SH , Oh YH , Song BK , Lee SH
Ref : Biotechnol Lett , 35 :1677 , 2013
Abstract : Microbial-surface display is the expression of proteins or peptides on the surface of cells by fusing an appropriate protein as an anchoring motif. Here, the outer membrane protein W (OmpW) was selected as a fusion partner for functional expression of Pseudomonas fluorescence SIK W1 lipase (TliA) on the cell-surface of Escherichia coli. Localization of the truncated OmpW-TliA fusion protein on the cell-surface was confirmed by immunoblotting and functional assay of lipase activity. Enantioselective hydrolysis of rac-phenylethyl butanoate by the displayed lipase resulted in optically active (R)-phenyl ethanol with 96 % enantiomeric excess and 44 % of conversion in 5 days. Thus, a small outer membrane protein OmpW, is a useful anchoring motif for displaying an active enzyme of ~50 kDa on the cell-surface and the surface-displayed lipase can be employed as an enantioselective biocatalyst in organic synthesis.
ESTHER : Lee_2013_Biotechnol.Lett_35_1677
PubMedSearch : Lee_2013_Biotechnol.Lett_35_1677
PubMedID: 23881313

Title : Lipase-catalyzed enantioselective synthesis of (R,R)-lactide from alkyl lactate to produce PDLA (poly D-lactic acid) and stereocomplex PLA (poly lactic acid) - Jeon_2013_J.Biotechnol_168_201
Author(s) : Jeon BW , Lee J , Kim HS , Cho DH , Lee H , Chang R , Kim YH
Ref : J Biotechnol , 168 :201 , 2013
Abstract : R-lactide, a pivotal monomer for the production of poly (D-lactic acid) (PDLA) or stereocomplex poly (lactic acid) (PLA) was synthesized from alkyl (R)-lactate through a lipase-catalyzed reaction without racemization. From among several types of lipase, only lipase B from Candida antarctica (Novozym 435; CAL-B) was effective in the reaction that synthesized (R,R)-lactide. Enantiopure (R,R)-lactide, which consisted of over 99% enantiomeric excess, was synthesized from methyl (R)-lactate through CAL-B catalysis. Removal of the methanol by-product was critical to obtain a high level of lactide conversion. The (R,R)-lactide yield was 56% in a reaction containing 100 mg of Novozym 435, 10 mM methyl (R)-lactate and 1500 mg of molecular sieve 5A in methyl tert-butyl ether (MTBE). The important monomer (R,R)-lactide that is required for the production of the widely recognized bio-plastic PDLA and the PLA stereocomplex can be obtained using this novel synthetic method.
ESTHER : Jeon_2013_J.Biotechnol_168_201
PubMedSearch : Jeon_2013_J.Biotechnol_168_201
PubMedID: 23845270
Gene_locus related to this paper: canar-LipB

Title : Whole-Genome Sequence of Mycobacterium intracellulare Clinical Strain MOTT-H4Y, Belonging to INT5 Genotype - Lee_2013_Genome.Announc_1_e00006
Author(s) : Lee H , Kim BJ , Kim K , Hong SH , Kook YH
Ref : Genome Announc , 1 : , 2013
Abstract : Here, we report the draft genome sequence of the Mycobacterium intracellulare clinical strain MOTT-H4Y, grouped previously into the INT5 genotype of the 5 genotypes of M. intracellulare.
ESTHER : Lee_2013_Genome.Announc_1_e00006
PubMedSearch : Lee_2013_Genome.Announc_1_e00006
PubMedID: 23472222
Gene_locus related to this paper: mycia-h8ivh5 , 9myco-j9waw2 , 9myco-l8khu2 , 9myco-i2acb5

Title : Crystal structure of the human N-Myc downstream-regulated gene 2 protein provides insight into its role as a tumor suppressor - Hwang_2011_J.Biol.Chem_286_12450
Author(s) : Hwang J , Kim Y , Kang HB , Jaroszewski L , Deacon AM , Lee H , Choi WC , Kim KJ , Kim CH , Kang BS , Lee JO , Oh TK , Kim JW , Wilson IA , Kim MH
Ref : Journal of Biological Chemistry , 286 :12450 , 2011
Abstract : Considerable attention has recently been paid to the N-Myc downstream-regulated gene (NDRG) family because of its potential as a tumor suppressor in many human cancers. Primary amino acid sequence information suggests that the NDRG family proteins may belong to the alpha/beta-hydrolase (ABH) superfamily; however, their functional role has not yet been determined. Here, we present the crystal structures of the human and mouse NDRG2 proteins determined at 2.0 and 1.7 A resolution, respectively. Both NDRG2 proteins show remarkable structural similarity to the ABH superfamily, despite limited sequence similarity. Structural analysis suggests that NDRG2 is a nonenzymatic member of the ABH superfamily, because it lacks the catalytic signature residues and has an occluded substrate-binding site. Several conserved structural features suggest NDRG may be involved in molecular interactions. Mutagenesis data based on the structural analysis support a crucial role for helix alpha6 in the suppression of TCF/beta-catenin signaling in the tumorigenesis of human colorectal cancer, via a molecular interaction.
ESTHER : Hwang_2011_J.Biol.Chem_286_12450
PubMedSearch : Hwang_2011_J.Biol.Chem_286_12450
PubMedID: 21247902
Gene_locus related to this paper: human-NDRG2

Title : High fat diet induced downregulation of microRNA-467b increased lipoprotein lipase in hepatic steatosis - Ahn_2011_Biochem.Biophys.Res.Commun_414_664
Author(s) : Ahn J , Lee H , Chung CH , Ha T
Ref : Biochemical & Biophysical Research Communications , 414 :664 , 2011
Abstract : Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation and is presently the most common chronic liver disease. However, the mechanisms underlying the development of steatosis remain unclear. MicroRNAs (miRNAs) are small non-coding RNAs that modulate a variety of biological functions. We have investigated the role of miRNA in the development of steatosis. We found that miR-467b expression is significantly downregulated in liver tissues of high-fat diet fed mice and in steatosis-induced hepatocytes. The downregulation of miR-467b resulted in the upregulation of hepatic lipoprotein lipase (LPL), the direct target of miR-467b. Moreover, the interaction between miR-467b and LPL was associated with insulin resistance, a major cause of NAFLD. These results suggest that downregulation of miR-467b is involved in the development of hepatic steatosis by modulating the expression of its target, LPL.
ESTHER : Ahn_2011_Biochem.Biophys.Res.Commun_414_664
PubMedSearch : Ahn_2011_Biochem.Biophys.Res.Commun_414_664
PubMedID: 21986524

Title : The effects of acupuncture (PC6) on chronic mild stress-induced memory loss - Kim_2011_Neurosci.Lett_488_225
Author(s) : Kim H , Park HJ , Shim HS , Han SM , Hahm DH , Lee H , Shim I
Ref : Neuroscience Letters , 488 :225 , 2011
Abstract : A previous study reported that the PC6 acupuncture point can alleviate chronic mild stress (CMS)-induced anxiety [17]. Following the previous study, this study examined the effects of the PC6 acupuncture point on CMS-induced memory loss. The memory storage and acetylcholinesterase (AchE) activity in the hippocampus were measured, respectively, using a passive avoidance test (PAT) and AchE immunohistochemistry. In the PAT (retention test), the CMS group showed a markedly lower latency time than the control (post (72h): P<0.01, post (96h): P<0.05, post (120h): P<0.001). However, acupuncture at PC6 significantly recovered the impairment of memory compared to the CMS group (post (120h): P<0.001). Exposure to CMS also significantly decreased the AchE activity in the hippocampus compared to the control rats. Acupuncture stimulation at the PC6 point on the pericardium channels (3min), but not at other points (TE5), produced memory improvements and an increase in AchE reactivity in the hippocampus compared to the CMS group. These results show that the acupuncture point is effective in restoring the CMS-related biochemical and behavioral impairments, such as learning and memory.
ESTHER : Kim_2011_Neurosci.Lett_488_225
PubMedSearch : Kim_2011_Neurosci.Lett_488_225
PubMedID: 20946936

Title : Genome sequence of Weissella thailandensis fsh4-2 - Benomar_2011_J.Bacteriol_193_5868
Author(s) : Benomar N , Abriouel H , Lee H , Cho GS , Huch M , Pulido RP , Holzapfel WH , Galvez A , Franz CM
Ref : Journal of Bacteriology , 193 :5868 , 2011
Abstract : Weissella thailandensis fsh4-2 is a heterofermentative lactic acid bacterium isolated from the Korean fermented seafood condiment jeotkal. Here we report the draft genome sequence of W. thailandensis fsh4-2 (1,651 genes, 1,436 encoding known proteins, 183 encoding unknown proteins, 32 RNA genes), which consists of 50 large contigs of >100 bp.
ESTHER : Benomar_2011_J.Bacteriol_193_5868
PubMedSearch : Benomar_2011_J.Bacteriol_193_5868
PubMedID: 21952542
Gene_locus related to this paper: 9lact-g0ugh9 , 9lact-g0ugc7

Title : The effect of pyridostigmine on bispectral index during recovery from sevoflurane anesthesia - Jeong_2011_Korean.J.Anesthesiol_61_460
Author(s) : Jeong SJ , Han JI , Baik HJ , Lee H , Lee GY , Kim JH
Ref : Korean J Anesthesiol , 61 :460 , 2011
Abstract : BACKGROUND: There have been some conflicting reports showing that muscle relaxants and anticholinesterases affect the level of the bispectral index (BIS). The purpose of this study was to investigate whether pyridostigmine affects the level of the BIS during recovery from sevoflurane anesthesia. METHODS: Fifty-two adult patients scheduled for laparoscopic cholecystectomy and laparoscopic appendectomy. Anesthesia was induced with thiopental 4 mg/kg and rocuronium 0.6 mg/kg. The lung was mechanically ventilated with 1-3 vol% sevoflurane, 50% oxygen and 50% nitrous oxide. After a specimen was removed, the sevoflurane concentration was maintained at 1.5 vol%. When skin closure began, sevoflurane was stopped; however, 50% oxygen and 50% nitrous oxide were maintained. The patients then received either (1) a group that received an injection of glycopyrrolate 0.04 mg/kg and pyridostigmine 0.2 mg/kg (reverse (R) group, n = 26) or (2) a group that received normal saline (control (C) group, n = 26). Group assignment was random. Pyridostigmine, a reversible cholinesterase inhibitor, is a parasympathomimetic. End-tidal sevoflurane concentration, train of four (TOF) ratio, bispectral index (BIS), blood pressure and heart rate were measured from the end of the operation to 15 min after inject of pyridostigmine or placebo. RESULTS: There were no significant between group differences in the time dependent decrease in end-tidal sevoflurane concentration (P = 0.0642). There were significant differences between the two groups for the time course for increases in the TOF value (P < 0.0001). There were significant differences between the two groups for the time course for increases in the BIS value (P = 0.0107). There were no significant differences in the mean BIS value up to 10 minutes after administering drug, but 15 minutes after administrating the reverse drug or the control drug, the BIS value showed significantly different BIS values: 68.2 +/- 6.2 (Group R) and 63.2 +/- 6.2 (Group C) (P = 0.0058). CONCLUSIONS: The finding that pyridostigmine increases TOF and BIS suggests that pyridostigmine may enhance recovery during recovery from sevoflurane anesthesia.
ESTHER : Jeong_2011_Korean.J.Anesthesiol_61_460
PubMedSearch : Jeong_2011_Korean.J.Anesthesiol_61_460
PubMedID: 22220221

Title : Functional and evolutionary insights from the genomes of three parasitoid Nasonia species - Werren_2010_Science_327_343
Author(s) : Werren JH , Richards S , Desjardins CA , Niehuis O , Gadau J , Colbourne JK , Beukeboom LW , Desplan C , Elsik CG , Grimmelikhuijzen CJ , Kitts P , Lynch JA , Murphy T , Oliveira DC , Smith CD , van de Zande L , Worley KC , Zdobnov EM , Aerts M , Albert S , Anaya VH , Anzola JM , Barchuk AR , Behura SK , Bera AN , Berenbaum MR , Bertossa RC , Bitondi MM , Bordenstein SR , Bork P , Bornberg-Bauer E , Brunain M , Cazzamali G , Chaboub L , Chacko J , Chavez D , Childers CP , Choi JH , Clark ME , Claudianos C , Clinton RA , Cree AG , Cristino AS , Dang PM , Darby AC , de Graaf DC , Devreese B , Dinh HH , Edwards R , Elango N , Elhaik E , Ermolaeva O , Evans JD , Foret S , Fowler GR , Gerlach D , Gibson JD , Gilbert DG , Graur D , Grunder S , Hagen DE , Han Y , Hauser F , Hultmark D , Hunter HCt , Hurst GD , Jhangian SN , Jiang H , Johnson RM , Jones AK , Junier T , Kadowaki T , Kamping A , Kapustin Y , Kechavarzi B , Kim J , Kiryutin B , Koevoets T , Kovar CL , Kriventseva EV , Kucharski R , Lee H , Lee SL , Lees K , Lewis LR , Loehlin DW , Logsdon JM, Jr. , Lopez JA , Lozado RJ , Maglott D , Maleszka R , Mayampurath A , Mazur DJ , McClure MA , Moore AD , Morgan MB , Muller J , Munoz-Torres MC , Muzny DM , Nazareth LV , Neupert S , Nguyen NB , Nunes FM , Oakeshott JG , Okwuonu GO , Pannebakker BA , Pejaver VR , Peng Z , Pratt SC , Predel R , Pu LL , Ranson H , Raychoudhury R , Rechtsteiner A , Reese JT , Reid JG , Riddle M , Robertson HM , Romero-Severson J , Rosenberg M , Sackton TB , Sattelle DB , Schluns H , Schmitt T , Schneider M , Schuler A , Schurko AM , Shuker DM , Simoes ZL , Sinha S , Smith Z , Solovyev V , Souvorov A , Springauf A , Stafflinger E , Stage DE , Stanke M , Tanaka Y , Telschow A , Trent C , Vattathil S , Verhulst EC , Viljakainen L , Wanner KW , Waterhouse RM , Whitfield JB , Wilkes TE , Williamson MS , Willis JH , Wolschin F , Wyder S , Yamada T , Yi SV , Zecher CN , Zhang L , Gibbs RA , Williamson M
Ref : Science , 327 :343 , 2010
Abstract : We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.
ESTHER : Werren_2010_Science_327_343
PubMedSearch : Werren_2010_Science_327_343
PubMedID: 20075255
Gene_locus related to this paper: nasvi-ACHE1 , nasvi-ACHE2 , nasvi-k7in31 , nasvi-k7iwl9 , nasvi-k7iyk8 , nasvi-k7jlv1 , nasvi-k7in32 , nasvi-k7ind2 , nasvi-k7inh0 , nasvi-k7inh1 , nasvi-k7inh2 , nasvi-k7inp9 , nasvi-k7iun7 , nasvi-k7iv21 , nasvi-k7ivn5 , nasvi-k7ivn6 , nasvi-k7iw29 , nasvi-k7iwk5 , nasvi-k7iwl8 , nasvi-k7iz24 , nasvi-k7izb4 , nasvi-k7j5u6 , nasvi-k7j6y1 , nasvi-k7j6y2 , nasvi-k7j6y4 , nasvi-k7j718 , nasvi-k7j755 , nasvi-k7j756 , nasvi-k7j757 , nasvi-k7j7k5 , nasvi-k7j7n7 , nasvi-k7j7r8 , nasvi-k7j7s8 , nasvi-k7j7s9 , nasvi-k7j811 , nasvi-k7iny8 , nasvi-k7izf2 , nasvi-k7iwe2 , nasvi-k7j6w4 , nasvi-k7izl9 , nasvi-k7jf39 , nasvi-k7izl8 , nasvi-k7irf1 , nasvi-k7j7l1

Title : Alternative splicing of neuroligin regulates the rate of presynaptic differentiation - Lee_2010_J.Neurosci_30_11435
Author(s) : Lee H , Dean C , Isacoff E
Ref : Journal of Neuroscience , 30 :11435 , 2010
Abstract : Neuroligins (NLGs) and Neurexins (NRXs) are important adhesion molecules that promote synapse formation. Multiple splice variants of NLG and NRX exist, but their specific functions are unclear. Here we report that a surrogate postsynaptic cell expressing full-length NLG-1 triggers slow presynaptic differentiation in a contacting axon. In contrast, a version of NLG-1, which lacks insert B (NLG-1DeltaB), induces rapid presynaptic differentiation, reaching the rate seen at native neuronal synapses. We show that this acceleration is attributed to the removal of the N-linked glycosylation site within insert B. NLG-1DeltaB also increases synaptic density at neuro-neuronal synapses more than does full-length NLG-1. Other postsynaptic adhesion proteins, such as N-cadherin, EphB2, and SynCAM-1, alone or in combination with full-length NLG-1, do not trigger fast differentiation, suggesting that rapid presynaptic differentiation depends on a unique interaction of NLG-1DeltaB with axonal proteins. Indeed, we find that NLG-1DeltaB recruits more axonal alpha-NRX. Our results suggest that the engagement of alpha-NRX is a key to rapid induction of synapses at new sites of axo-dendritic contact.
ESTHER : Lee_2010_J.Neurosci_30_11435
PubMedSearch : Lee_2010_J.Neurosci_30_11435
PubMedID: 20739565

Title : The B73 maize genome: complexity, diversity, and dynamics - Schnable_2009_Science_326_1112
Author(s) : Schnable PS , Ware D , Fulton RS , Stein JC , Wei F , Pasternak S , Liang C , Zhang J , Fulton L , Graves TA , Minx P , Reily AD , Courtney L , Kruchowski SS , Tomlinson C , Strong C , Delehaunty K , Fronick C , Courtney B , Rock SM , Belter E , Du F , Kim K , Abbott RM , Cotton M , Levy A , Marchetto P , Ochoa K , Jackson SM , Gillam B , Chen W , Yan L , Higginbotham J , Cardenas M , Waligorski J , Applebaum E , Phelps L , Falcone J , Kanchi K , Thane T , Scimone A , Thane N , Henke J , Wang T , Ruppert J , Shah N , Rotter K , Hodges J , Ingenthron E , Cordes M , Kohlberg S , Sgro J , Delgado B , Mead K , Chinwalla A , Leonard S , Crouse K , Collura K , Kudrna D , Currie J , He R , Angelova A , Rajasekar S , Mueller T , Lomeli R , Scara G , Ko A , Delaney K , Wissotski M , Lopez G , Campos D , Braidotti M , Ashley E , Golser W , Kim H , Lee S , Lin J , Dujmic Z , Kim W , Talag J , Zuccolo A , Fan C , Sebastian A , Kramer M , Spiegel L , Nascimento L , Zutavern T , Miller B , Ambroise C , Muller S , Spooner W , Narechania A , Ren L , Wei S , Kumari S , Faga B , Levy MJ , McMahan L , Van Buren P , Vaughn MW , Ying K , Yeh CT , Emrich SJ , Jia Y , Kalyanaraman A , Hsia AP , Barbazuk WB , Baucom RS , Brutnell TP , Carpita NC , Chaparro C , Chia JM , Deragon JM , Estill JC , Fu Y , Jeddeloh JA , Han Y , Lee H , Li P , Lisch DR , Liu S , Liu Z , Nagel DH , McCann MC , SanMiguel P , Myers AM , Nettleton D , Nguyen J , Penning BW , Ponnala L , Schneider KL , Schwartz DC , Sharma A , Soderlund C , Springer NM , Sun Q , Wang H , Waterman M , Westerman R , Wolfgruber TK , Yang L , Yu Y , Zhang L , Zhou S , Zhu Q , Bennetzen JL , Dawe RK , Jiang J , Jiang N , Presting GG , Wessler SR , Aluru S , Martienssen RA , Clifton SW , McCombie WR , Wing RA , Wilson RK
Ref : Science , 326 :1112 , 2009
Abstract : We report an improved draft nucleotide sequence of the 2.3-gigabase genome of maize, an important crop plant and model for biological research. Over 32,000 genes were predicted, of which 99.8% were placed on reference chromosomes. Nearly 85% of the genome is composed of hundreds of families of transposable elements, dispersed nonuniformly across the genome. These were responsible for the capture and amplification of numerous gene fragments and affect the composition, sizes, and positions of centromeres. We also report on the correlation of methylation-poor regions with Mu transposon insertions and recombination, and copy number variants with insertions and/or deletions, as well as how uneven gene losses between duplicated regions were involved in returning an ancient allotetraploid to a genetically diploid state. These analyses inform and set the stage for further investigations to improve our understanding of the domestication and agricultural improvements of maize.
ESTHER : Schnable_2009_Science_326_1112
PubMedSearch : Schnable_2009_Science_326_1112
PubMedID: 19965430
Gene_locus related to this paper: maize-b4ffc7 , maize-b6u7e1 , maize-c0pcy5 , maize-c0pgf7 , maize-c0pgw1 , maize-c0pfl3 , maize-b4fpr7 , maize-k7vy73 , maize-a0a096swr3 , maize-k7v3i9 , maize-b6u9v9 , maize-a0a3l6e780 , maize-b4fv80 , maize-a0a1d6nse2 , maize-c4j9a1 , maize-k7uba1

Title : Adenoviral gene transfer of acetylcholinesterase T subunit in the hypothalamus potentiates electroacupuncture analgesia in rats - Kim_2009_Genes.Brain.Behav_8_174
Author(s) : Kim SK , Park JY , Koo BH , Lee JH , Kim HS , Choi WK , Shim I , Lee H , Hong MC , Shin MK , Min BI , Bae H
Ref : Genes Brain Behav , 8 :174 , 2009
Abstract : Our previous studies, using cDNA microarray and real-time reverse transcription-polymerase chain reaction, showed that acetylcholinesterase T subunit (AChET) gene was more abundantly expressed in the hypothalamus of the responder rats that were sensitive to electroacupuncture (EA) in the tail flick latency (TFL) test than in that of the non-responder rats that were insensitive to EA. In this study, we hypothesized that the expression of the AChET gene in the hypothalamus modulates EA analgesia in rats. To explore the hypothesis, we constructed an AChET-encoding adenovirus and a control virus expressing only green fluorescence protein, either of which was then injected into the hypothalamus of Sprague-Dawley rats. The hypothalamic activity of acetylcholinesterase was significantly higher in rats that were injected with the AChET virus than in rats that were injected with the control virus. The basal pain threshold measured by a TFL test was not changed by microinjection of AChET or control virus into the hypothalamus when EA treatment was not conducted. However, the analgesic effect of EA was significantly enhanced from 7 days after microinjection of the AChET virus into the hypothalamus but not after injection of the control virus. Furthermore, expression of the AChET in the hypothalamus did not affect body core temperature, body weight, motor function or learning and memory ability. Taken together, these results suggest that adenoviral expression of the AChET gene in the hypothalamus potentiates EA analgesia in rats without apparent side-effects.
ESTHER : Kim_2009_Genes.Brain.Behav_8_174
PubMedSearch : Kim_2009_Genes.Brain.Behav_8_174
PubMedID: 19077179

Title : Human plasma carboxylesterase 1, a novel serologic biomarker candidate for hepatocellular carcinoma - Na_2009_Proteomics_9_3989
Author(s) : Na K , Lee EY , Lee HJ , Kim KY , Lee H , Jeong SK , Jeong AS , Cho SY , Kim SA , Song SY , Kim KS , Cho SW , Kim H , Paik YK
Ref : Proteomics , 9 :3989 , 2009
Abstract : To identify and characterize a serologic glycoprotein biomarker for hepatocellular carcinoma (HCC), multi-lectin affinity chromatography was used to isolate intracellular N-linked glycoprotein fractions from five paired non-tumor and tumor tissues. From the series of 2-D DIGE targeted differentially expressed N-linked glycoproteins, we identified human liver carboxylesterase 1 (hCE1), which was remarkably down-regulated in tumor tissues, a finding confirmed by Western blot, a quantitative real-time RT-PCR, and immunohistochemical staining of non-tumor and tumor tissues from total 58 HCC patients. To investigate whether hCE1 is also present in human plasma, we employed a magnetic bead-based immunoprecipitation followed by nano-LC-MS/MS analysis, and we found for the first time that hCE1 is present in human plasma as opposed to that in liver tissues. That is, from normalization of hCE1 signal by the immunoprecipitation and Western blot analysis, hCE1 levels were increased in plasma specimens from HCC patients than in plasma from other disease patient groups (e.g. liver cirrhosis, chronic hepatitis, cholangiocarcinoma, stomach cancer, and pancreatic cancer). From the receiver operating characteristic analysis in HCC, both sensitivity and specificity were shown to be greater than 70.0 and 85.0%, respectively. Thus, the high-resolution proteomic approach demonstrates that hCE1 is a good candidate for further validation as a serologic glycoprotein biomarker for HCC.
ESTHER : Na_2009_Proteomics_9_3989
PubMedSearch : Na_2009_Proteomics_9_3989
PubMedID: 19658107
Gene_locus related to this paper: human-CES1

Title : Evolution and expansion of the Mycobacterium tuberculosis PE and PPE multigene families and their association with the duplication of the ESAT-6 (esx) gene cluster regions - Gey van Pittius_2006_BMC.Evol.Biol_6_95
Author(s) : Gey van Pittius NC , Sampson SL , Lee H , Kim Y , van Helden PD , Warren RM
Ref : BMC Evol Biol , 6 :95 , 2006
Abstract : BACKGROUND: The PE and PPE multigene families of Mycobacterium tuberculosis comprise about 10% of the coding potential of the genome. The function of the proteins encoded by these large gene families remains unknown, although they have been proposed to be involved in antigenic variation and disease pathogenesis. Interestingly, some members of the PE and PPE families are associated with the ESAT-6 (esx) gene cluster regions, which are regions of immunopathogenic importance, and encode a system dedicated to the secretion of members of the potent T-cell antigen ESAT-6 family. This study investigates the duplication characteristics of the PE and PPE gene families and their association with the ESAT-6 gene clusters, using a combination of phylogenetic analyses, DNA hybridization, and comparative genomics, in order to gain insight into their evolutionary history and distribution in the genus Mycobacterium. RESULTS: The results showed that the expansion of the PE and PPE gene families is linked to the duplications of the ESAT-6 gene clusters, and that members situated in and associated with the clusters represent the most ancestral copies of the two gene families. Furthermore, the emergence of the repeat protein PGRS and MPTR subfamilies is a recent evolutionary event, occurring at defined branching points in the evolution of the genus Mycobacterium. These gene subfamilies are thus present in multiple copies only in the members of the M. tuberculosis complex and close relatives. The study provides a complete analysis of all the PE and PPE genes found in the sequenced genomes of members of the genus Mycobacterium such as M. smegmatis, M. avium paratuberculosis, M. leprae, M. ulcerans, and M. tuberculosis. CONCLUSION: This work provides insight into the evolutionary history for the PE and PPE gene families of the mycobacteria, linking the expansion of these families to the duplications of the ESAT-6 (esx) gene cluster regions, and showing that they are composed of subgroups with distinct evolutionary (and possibly functional) differences.
ESTHER : Gey van Pittius_2006_BMC.Evol.Biol_6_95
PubMedSearch : Gey van Pittius_2006_BMC.Evol.Biol_6_95
PubMedID: 17105670

Title : Neuronal synapse interaction reconstituted between live cells and supported lipid bilayers - Pautot_2005_Nat.Chem.Biol_1_283
Author(s) : Pautot S , Lee H , Isacoff EY , Groves JT
Ref : Nat Chemical Biology , 1 :283 , 2005
Abstract : In the nervous system, homophilic and heterophilic adhesion molecules participate in the induction and differentiation of presynaptic transmitter release sites. We focus on the heterophilic interaction between postsynaptic neuroligin-1 (Nlg) and presynaptic beta-neurexin (Nrx). Nlg has previously been shown to trigger presynaptic differentiation in a Nrx-expressing axon even when presented on a non-neuronal cell or on beads coated with lipid bilayers. We have now developed a new method to measure single molecule and ensemble distribution of Nrx and Nlg at the contact site between a non-neuronal Nrx-expressing cell and a flat supported glycosylphosphoinositol-neuroligin-1 (GPI-Nlg) lipid bilayer and relate them to adhesion as measured by cell migration and gravity dissociation. We find that within minutes after cell-bilayer contact, Nrx accumulates at the contact site and the contact area is expanded. The strength of cell-bilayer adhesion depends on the morphology of Nrx accumulation, with the focal concentration strengthening adhesion. The results suggest that Nlg-Nrx interaction rapidly establishes a weak, but specific, adhesion between dynamic pre- and postsynaptic processes, which may ultimately require additional molecules for synapse stabilization.
ESTHER : Pautot_2005_Nat.Chem.Biol_1_283
PubMedSearch : Pautot_2005_Nat.Chem.Biol_1_283
PubMedID: 16408058

Title : Psychoactive drugs and pilot performance: a comparison of nicotine, donepezil, and alcohol effects - Mumenthaler_2003_Neuropsychopharmacology_28_1366
Author(s) : Mumenthaler MS , Yesavage JA , Taylor JL , O'Hara R , Friedman L , Lee H , Kraemer HC
Ref : Neuropsychopharmacology , 28 :1366 , 2003
Abstract : The cholinergic system plays a major role in cognitive abilities that are essential to piloting an aircraft: attention, learning, and memory. In previous studies, drugs that enhance the cholinergic system through different pharmacologic mechanisms have shown beneficial effects on cognition; but dissimilar cognitive measures were used and samples were not comparable. A comparison within the same cognitive tasks, within comparable samples appears desirable. Toward this aim, we compared effect sizes (ES) of performance-enhancing doses of nicotine (a nicotinic receptor agonist) and donepezil (an acetylcholinesterase inhibitor) as found in our prior work on pilot performance. We also compared cholinergic ES to those of performance-impairing doses of alcohol. In three randomized, placebo-controlled trials, we assessed the flight performance of aircraft pilots in a Frasca 141 simulator, testing I: the acute effects of nicotine gum 2 mg; II: the effects of administration of 5 mg donepezil/day for 30 days; and III: the acute and 8 h-carryover effects of alcohol after a target peak BAC of 0.10%. We calculated the ES of nicotine, donepezil, and alcohol on a flight summary score and on four flight component scores. Compared to placebo, nicotine and donepezil significantly improved, while alcohol significantly impaired overall flight performance: ES (nicotine)=0.80; ES (donepezil)=1.02; ES (alcohol acute)=-3.66; ES (alcohol 8 h)=-0.82. Both cholinergic drugs showed the largest effects on flight tasks requiring sustained visual attention. Although the two tested cholinergic drugs have different pharmacologic mechanisms, their effects on flight performance were similar in kind and size. The beneficial effects of the cholinergic drugs on overall flight performance were large and the absolute (ie nondirectional) sizes were about one-fourth of the absolute ES of acute alcohol intoxication and roughly the same as the absolute 8 h-carryover ES of alcohol.
ESTHER : Mumenthaler_2003_Neuropsychopharmacology_28_1366
PubMedSearch : Mumenthaler_2003_Neuropsychopharmacology_28_1366
PubMedID: 12784106

Title : Colorimetric assay for Lindane dechlorination by bacteria - Phillips_2001_J.Microbiol.Methods_47_181
Author(s) : Phillips TM , Seech AG , Lee H , Trevors JT
Ref : J Microbiol Methods , 47 :181 , 2001
Abstract : A colorimetric microtitre plate-based assay that detects haloalkane dehalogenase activity was modified to detect dechlorination of gamma-hexachlorocyclohexane (Lindane). Dechlorination is indicated by the colour change of phenol red from red to yellow, in a weakly buffered solution, as the solution becomes acidic due to HCl formed during dechlorination. Enzyme activity can be monitored by reading the absorbance of each well at 540 nm. Positive controls for the assay were the known Lindane-degrading microorganisms, Rhodanobacter lindaniclasticus and Sphingomonas paucimobilis UT26. Dechlorination in a scaled-up version of the assay was confirmed by GC/ECD detection of known metabolites of the test microorganisms from which the enzyme extracts were prepared. The assay was used to measure the rate of dechlorination in cell-free extracts of R. lindaniclasticus. It was also used to screen the cell-free extracts of 24 bacterial isolates, from a Lindane-contaminated soil, for Lindane dechlorination activity. Although no isolates tested positive, the assay represents a new inexpensive and rapid screening tool for the detection of Lindane-degrading microorganisms.
ESTHER : Phillips_2001_J.Microbiol.Methods_47_181
PubMedSearch : Phillips_2001_J.Microbiol.Methods_47_181
PubMedID: 11576682

Title : Vesicular localization and characterization of a novel post-proline-cleaving aminodipeptidase, quiescent cell proline dipeptidase. -
Author(s) : Chiravuri M , Agarraberes F , Mathieu SL , Lee H , Huber BT
Ref : J Immunol , 165 :5695 , 2000
PubMedID: 11067927
Gene_locus related to this paper: human-DPP7

Title : Association of CYP1A1 and microsomal epoxide hydrolase polymorphisms with lung squamous cell carcinoma - Lin_2000_Br.J.Cancer_82_852
Author(s) : Lin P , Wang SL , Wang HJ , Chen KW , Lee HS , Tsai KJ , Chen CY , Lee H
Ref : Br J Cancer , 82 :852 , 2000
Abstract : Lung cancer is the leading cause of death among cancers in Taiwan. Although the etiology of lung cancer has yet to be defined, genetic variability in activities of metabolic enzymes has been correlated with lung cancer. In the present study, the possibility of association of CYP1A1 and microsomal epoxide hydrolase (HYL1) genetic polymorphisms with lung cancer was examined among 132 lung cancer patients and 259 controls in Taiwan. No significant association was observed for either CYP1A1 or HYL1 polymorphism alone and the overall incidence of lung cancer after adjusting for age, gender and smoking status. When cases were stratified according to histological type, there was significant association between CYP1A1*2A homozygote and squamous cell carcinoma (SCC) (odds ratio (OR) 2.86; 95% confidence interval (CI) 1.33-6.12). Similarly, the proportion of HYL1 genotypes corresponding to high or normal enzyme activities was higher in SCC than in controls (OR 1.96; 95% CI 1.04-3.70). A combination of susceptible CYP1A1 and HYL1 genotypes was found to be highly associated with lung cancer, especially with SCC (OR 6.76; 95% CI 2.29-19.10). Our results suggest that the combination of CYP1A1 and HYL1 polymorphisms is an important risk factor for lung SCC.
ESTHER : Lin_2000_Br.J.Cancer_82_852
PubMedSearch : Lin_2000_Br.J.Cancer_82_852
PubMedID: 10732758

Title : Sequence, purification, and cloning of an intracellular serine protease, quiescent cell proline dipeptidase - Underwood_1999_J.Biol.Chem_274_34053
Author(s) : Underwood R , Chiravuri M , Lee H , Schmitz T , Kabcenell AK , Yardley K , Huber BT
Ref : Journal of Biological Chemistry , 274 :34053 , 1999
Abstract : We recently observed that specific inhibitors of post-proline cleaving aminodipeptidases cause apoptosis in quiescent lymphocytes in a process independent of CD26/dipeptidyl peptidase IV. These results led to the isolation and cloning of a new protease that we have termed quiescent cell proline dipeptidase (QPP). QPP activity was purified from CD26(-) Jurkat T cells. The protein was identified by labeling with [(3)H]diisopropylfluorophosphate and subjected to tryptic digestion and partial amino acid sequencing. The peptide sequences were used to identify expressed sequence tag clones. The cDNA of QPP contains an open reading frame of 1476 base pairs, coding for a protein of 492 amino acids. The amino acid sequence of QPP reveals similarity with prolylcarboxypeptidase. The putative active site residues serine, aspartic acid, and histidine of QPP show an ordering of the catalytic triad similar to that seen in the post-proline cleaving exopeptidases prolylcarboxypeptidase and CD26/dipeptidyl peptidase IV. The post-proline cleaving activity of QPP has an unusually broad pH range in that it is able to cleave substrate molecules at acidic pH as well as at neutral pH. QPP has also been detected in nonlymphocytic cell lines, indicating that this enzyme activity may play an important role in other tissues as well.
ESTHER : Underwood_1999_J.Biol.Chem_274_34053
PubMedSearch : Underwood_1999_J.Biol.Chem_274_34053
PubMedID: 10567372
Gene_locus related to this paper: human-DPP7

Title : Alteration of the substrate range of haloalkane dehalogenase by site-directed mutagenesis - Holloway_1998_Biotechnol.Bioeng_59_520
Author(s) : Holloway P , Knoke KL , Trevors JT , Lee H
Ref : Biotechnol Bioeng , 59 :520 , 1998
Abstract : We attempted to expand the range of chlorinated solvents degraded by Xanthobacter autotrophicus GJ10 to include trichloroethylene by the rational modification of the enzyme haloalkane dehalogenase. The amino acids Phe164, Asp170, Phe172 and Trp175 were individually replaced with alanine by site-directed mutagenesis. All substitutions produced enzymes with lower than wild type activity with 1,2-dichloroethane. The Phe164Ala and Asp170Ala mutants were 3 and 2 times more active than was the wild type enzyme in dechlorinating 1,6-dichlorohexane. The Asp170Ala mutant resembled the wild type enzyme in its relative activity against longer chain substrates. No mutant was active with trichloroethylene.
ESTHER : Holloway_1998_Biotechnol.Bioeng_59_520
PubMedSearch : Holloway_1998_Biotechnol.Bioeng_59_520
PubMedID: 10099367

Title : Complete genome sequence of Methanobacterium thermoautotrophicum deltaH: functional analysis and comparative genomics - Smith_1997_J.Bacteriol_179_7135
Author(s) : Smith DR , Doucette-Stamm LA , Deloughery C , Lee H , Dubois J , Aldredge T , Bashirzadeh R , Blakely D , Cook R , Gilbert K , Harrison D , Hoang L , Keagle P , Lumm W , Pothier B , Qiu D , Spadafora R , Vicaire R , Wang Y , Wierzbowski J , Gibson R , Jiwani N , Caruso A , Bush D , Reeve JN , et al.
Ref : Journal of Bacteriology , 179 :7135 , 1997
Abstract : The complete 1,751,377-bp sequence of the genome of the thermophilic archaeon Methanobacterium thermoautotrophicum deltaH has been determined by a whole-genome shotgun sequencing approach. A total of 1,855 open reading frames (ORFs) have been identified that appear to encode polypeptides, 844 (46%) of which have been assigned putative functions based on their similarities to database sequences with assigned functions. A total of 514 (28%) of the ORF-encoded polypeptides are related to sequences with unknown functions, and 496 (27%) have little or no homology to sequences in public databases. Comparisons with Eucarya-, Bacteria-, and Archaea-specific databases reveal that 1,013 of the putative gene products (54%) are most similar to polypeptide sequences described previously for other organisms in the domain Archaea. Comparisons with the Methanococcus jannaschii genome data underline the extensive divergence that has occurred between these two methanogens; only 352 (19%) of M. thermoautotrophicum ORFs encode sequences that are >50% identical to M. jannaschii polypeptides, and there is little conservation in the relative locations of orthologous genes. When the M. thermoautotrophicum ORFs are compared to sequences from only the eucaryal and bacterial domains, 786 (42%) are more similar to bacterial sequences and 241 (13%) are more similar to eucaryal sequences. The bacterial domain-like gene products include the majority of those predicted to be involved in cofactor and small molecule biosyntheses, intermediary metabolism, transport, nitrogen fixation, regulatory functions, and interactions with the environment. Most proteins predicted to be involved in DNA metabolism, transcription, and translation are more similar to eucaryal sequences. Gene structure and organization have features that are typical of the Bacteria, including genes that encode polypeptides closely related to eucaryal proteins. There are 24 polypeptides that could form two-component sensor kinase-response regulator systems and homologs of the bacterial Hsp70-response proteins DnaK and DnaJ, which are notably absent in M. jannaschii. DNA replication initiation and chromosome packaging in M. thermoautotrophicum are predicted to have eucaryal features, based on the presence of two Cdc6 homologs and three histones; however, the presence of an ftsZ gene indicates a bacterial type of cell division initiation. The DNA polymerases include an X-family repair type and an unusual archaeal B type formed by two separate polypeptides. The DNA-dependent RNA polymerase (RNAP) subunits A', A", B', B" and H are encoded in a typical archaeal RNAP operon, although a second A' subunit-encoding gene is present at a remote location. There are two rRNA operons, and 39 tRNA genes are dispersed around the genome, although most of these occur in clusters. Three of the tRNA genes have introns, including the tRNAPro (GGG) gene, which contains a second intron at an unprecedented location. There is no selenocysteinyl-tRNA gene nor evidence for classically organized IS elements, prophages, or plasmids. The genome contains one intein and two extended repeats (3.6 and 8.6 kb) that are members of a family with 18 representatives in the M. jannaschii genome.
ESTHER : Smith_1997_J.Bacteriol_179_7135
PubMedSearch : Smith_1997_J.Bacteriol_179_7135
PubMedID: 9371463
Gene_locus related to this paper: metth-metx , metth-MTH354

Title : Bis-catechol-substituted redox-reactive analogues of hexamethonium and decamethonium: stimulated affinity-dependent reactivity through iron peroxide catalysis - Gu_1994_J.Med.Chem_37_4417
Author(s) : Gu Y , Lee H , Hudson RA
Ref : Journal of Medicinal Chemistry , 37 :4417 , 1994
Abstract : Symmetrically bis-catechol-substituted analogues (1 and 2, respectively) of hexamethonium and decamethonium were synthesized and investigated as redox-activated affinity reagents toward the neurotoxin-binding sites of the nicotinic acetylcholine receptor (nAcChR), purified from Torpedo californica electroplax. These reagents bound to nAcChR with Kd = 1.8 x 10(-8) and 2.3 x 10(-7) M for 1 and 2, respectively. In the presence of a metal, Fe(II)/Fe(III), and peroxide, both reagents produced a rapid and efficient half-of-sites inactivation of neurotoxin-binding sites in the nAcChR in a concentration-dependent manner, which paralleled the extent of receptor binding of the reagents. In the absence of Fe(II)/Fe(III) peroxide, redox-dependent inactivation occurred for both 1 and 2 more slowly and only at concentrations much higher (10(3)-10(4) times) than those necessary to produce significant binding to nAcChR. However, receptor inactivation in the absence of added metal peroxide was still more efficient for 1 and 2 than observed previously for [(trimethylammonio)methyl]catechol (3), the prototypic redox-dependent affinity reagent after which 1 and 2 were patterned. Thus, the new reagents reported are expected to provide more efficient and selective conditions for redox-dependent inactivation at nAcChR and other macromolecular sites to which such reagents may be directed.
ESTHER : Gu_1994_J.Med.Chem_37_4417
PubMedSearch : Gu_1994_J.Med.Chem_37_4417
PubMedID: 7996555

Title : Mechanism of action of the redox affinity reagent [(trimethylammonio)methyl]catechol - Gu_1994_Biochemistry_33_8486
Author(s) : Gu Y , Lee H , Kirchhoff JR , Manzey L , Hudson RA
Ref : Biochemistry , 33 :8486 , 1994
Abstract : The synthesis of 4- and 5-hydroxy-3-[(trimethylammonio)methyl]catechol (4- and 5-HTMC) was carried out to examine their proposed involvement as intermediates in the spontaneous redox-dependent half-of-sites inactivation of neurotoxin binding sites in the nicotinic acetylcholine receptor (nAcChR) mediated by the parent compound 3-[(trimethylammonio)methyl]catechol (TMC) [Nickoloff et al. (1985) Biochemistry 24, 999-1007]. Oxidation of 4- and 5-HTMC occurred with sodium periodate with facile conversion to the corresponding p-quinones which were intercepted with thiols and cyclopentadiene. Both 4- and 5-HTMC inactivated neurotoxin binding in the nAcChR in a time course and over a concentration range consistent with their involvement as intermediates in the TMC redox-dependent inactivation of neurotoxin ([125I]-alpha-bungarotoxin) binding sites. Rapid concentration-dependent inactivation of neurotoxin sites occurred over a 10-1000 microM range and was resistant to further inactivation after 50% loss of available toxin binding sites on the nAcChR. Both 4- and 5-HTMC inactivated nAcChR neurotoxin sites much more rapidly and efficiently than was observed previously with TMC. The apparent binding constants for 4- and 5-HTMC with the nAcChR, calculated from their concentration-dependent inactivation behavior toward toxin binding sites, were Kd = 224 +/- 98 and 39 +/- 17 microM, respectively. The observed results and the redox potentials (vs Ag/AgCl reference electrode) measured by cyclic voltammetry at pH 1.8 for TMC (719 mV) and the 4- and 5-HTMC derivatives (519 and 443 mV, respectively) supported the previously proposed mechanism for inactivation of the nAcChR by TMC.
ESTHER : Gu_1994_Biochemistry_33_8486
PubMedSearch : Gu_1994_Biochemistry_33_8486
PubMedID: 8031782