Park SY

References (33)

Title : Evaluation of the Drug-Induced Liver Injury Potential of Saxagliptin through Reactive Metabolite Identification in Rats - Kim_2024_Pharmaceutics_16_
Author(s) : Kim KY , Jeong YJ , Park SY , Park EJ , Jeon JH , Song IS , Liu KH
Ref : Pharmaceutics , 16 : , 2024
Abstract : A liver injury was recently reported for saxagliptin, which is a dipeptidyl peptidase-4 (DPP-4) inhibitor. However, the underlying mechanisms of saxagliptin-induced liver injury remain unknown. This study aimed to evaluate whether saxagliptin, a potent and selective DPP-4 inhibitor that is globally used for treating type 2 diabetes mellitus, binds to the nucleophiles in vitro. Four DPP-4 inhibitors, including vildagliptin, were evaluated for comparison. Only saxagliptin and vildagliptin, which both contain a cyanopyrrolidine group, quickly reacted with L-cysteine to enzyme-independently produce thiazolinic acid metabolites. This saxagliptin-cysteine adduct was also found in saxagliptin-administered male Sprague-Dawley rats. In addition, this study newly identified cysteinyl glycine conjugates of saxagliptin and 5-hydroxysaxagliptin. The observed metabolic pathways were hydroxylation and conjugation with cysteine, glutathione, sulfate, and glucuronide. In summary, we determined four new thiazoline-containing thiol metabolites (cysteine and cysteinylglycine conjugates of saxagliptin and 5-hydroxysaxagliptin) in saxagliptin-administered male rats. Our results reveal that saxagliptin can covalently bind to the thiol groups of cysteine residues of endogenous proteins in vivo, indicating the potential for saxagliptin to cause drug-induced liver injury.
ESTHER : Kim_2024_Pharmaceutics_16_
PubMedSearch : Kim_2024_Pharmaceutics_16_
PubMedID: 38258116

Title : Electrochemical and fluorescent dual-mode sensor of acetylcholinesterase activity and inhibition based on MnO(2)@PD-coated surface - Kim_2023_Anal.Chim.Acta_1257_341171
Author(s) : Kim SG , Lee HK , Subba SH , Oh MH , Lee G , Park SY
Ref : Anal Chim Acta , 1257 :341171 , 2023
Abstract : We developed an electrochemical and fluorescent dual-mode sensor for assessing acetylcholinesterase (AChE) activity and inhibition by taking advantage of the high redox sensitivity of surface-coated mesoporous MnO(2)@polymer dot (MnO(2)@PD) towards AChE. The following phenomena constitute the basis of the detection mechanism: fluorescence resonance energy transfer (FRET) effect between MnO(2) and PD; catalytic hydrolysis of acetylthiocholine (ATCh) to thiocholine (TCh) by AChE expressed by PC-12 cells, inducing fluorescence restoration and change in the conductivity of the system due to MnO(2) decomposition; the presence of the inhibitor neostigmine preventing the conversion of ATCh to TCh. The surface-coated biosensor presents both fluorescence-based and electrochemical approaches for effectively monitoring AChE activity and inhibition. The fluorescence approach is based on the fluorescent "on/off" property of the system caused by MnO(2) breakdown after interaction with TCh and the subsequent release of PDs. The conductivity of the coated electrode decreased dramatically as AChE concentration increased, resulting in electrochemical sensing of AChE activity and inhibition screening. Real-time wireless sensing can be conducted using a smartphone to monitor the resistance change, investigating the potential use of MnO(2)@PD nanocomposites in biological studies, and offering a real-time redox-fluorescent test for AChE activity monitoring and inhibitor screening.
ESTHER : Kim_2023_Anal.Chim.Acta_1257_341171
PubMedSearch : Kim_2023_Anal.Chim.Acta_1257_341171
PubMedID: 37062569

Title : Neuroprotective Effects of Davallia mariesii Roots and Its Active Constituents on Scopolamine-Induced Memory Impairment in In Vivo and In Vitro Studies - Lee_2023_Pharmaceuticals.(Basel)_16_
Author(s) : Lee CH , Ko MS , Kim YS , Ham JE , Choi JY , Hwang KW , Park SY
Ref : Pharmaceuticals (Basel) , 16 : , 2023
Abstract : Beta-amyloid (Abeta) proteins, major contributors to Alzheimer's disease (AD), are overproduced and accumulate as oligomers and fibrils. These protein accumulations lead to significant changes in neuronal structure and function, ultimately resulting in the neuronal cell death observed in AD. Consequently, substances that can inhibit Abeta production and/or accumulation are of great interest for AD prevention and treatment. In the course of an ongoing search for natural products, the roots of Davallia mariesii T. Moore ex Baker were selected as a promising candidate with anti-amyloidogenic effects. The ethanol extract of D. mariesii roots, along with its active constituents, not only markedly reduced Abeta production by decreasing beta-secretase expression in APP-CHO cells (Chinese hamster ovary cells which stably express amyloid precursor proteins), but also exhibited the ability to diminish Abeta aggregation while enhancing the disaggregation of Abeta aggregates, as determined through the Thioflavin T (Th T) assay. Furthermore, in an in vivo study, the extract of D. mariesii roots showed potential (a tendency) for mitigating scopolamine-induced memory impairment, as evidenced by results from the Morris water maze test and the passive avoidance test, which correlated with reduced Abeta deposition. Additionally, the levels of acetylcholine were significantly elevated, and acetylcholinesterase levels significantly decreased in the brains of mice (whole brains). The treatment with the extract of D. mariesii roots also led to upregulated brain-derived neurotrophic factor (BDNF) and phospho-cAMP response element-binding protein (p-CREB) in the hippocampal region. These findings suggest that the extract of D. mariesii roots, along with its active constituents, may offer neuroprotective effects against AD. Consequently, there is potential for the development of the extract of D. mariesii roots and its active constituents as effective therapeutic or preventative agents for AD.
ESTHER : Lee_2023_Pharmaceuticals.(Basel)_16_
PubMedSearch : Lee_2023_Pharmaceuticals.(Basel)_16_
PubMedID: 38004471

Title : In-depth Proteomic Signature of Parathyroid Carcinoma - Kong_2023_Eur.J.Endocrinol__
Author(s) : Kong SH , Lee JH , Bae JM , Hong N , Kim H , Park SY , Choi YJ , Lee S , Rhee Y , Kim SW , Han D , Kim JH , Shin CS
Ref : European Journal of Endocrinology , : , 2023
Abstract : OBJECTIVE: Diagnosing parathyroid carcinoma (PC) is complicated and controversial that early diagnosis and intervention are often difficult. Therefore, we aimed to elucidate the protein signatures of PC through quantitative proteomic analyses to aid in the early and accurate diagnosis of PC. DESIGN: Retrospective cohort study. METHODS: We performed liquid chromatography with tandem mass spectrometry using formalin-fixed paraffin-embedded samples. For the analyses, 23 PC and 15 parathyroid adenoma (PA) tissues were collected from 6 tertiary hospitals in South Korea. RESULTS: The mean age of the patients was 52 years, and 63% were women. Proteomic expression profiling revealed 304 differentially expressed proteins (DEPs) with a cutoff of p < 0.05, and fold change >1.5. Among DEPs, we identified a set of 5 proteins that can discriminate PC from PA: carbonic anhydrase 4 [CA4], alpha/beta hydrolase domain-containing protein 14B [ABHD14B], laminin subunit beta-2 [LAMB2], CD44 antigen [CD44], and alpha-1-acid glycoprotein 1 [ORM1], that exhibited the highest area under the curve of 0.991 in neural network model. The nuclear percentage of CA4 and LAMB2 in immunohistochemistry were significantly lower in PC tissue than in the PA (CA4: 2.77 +/- 1.96%, 26.2 +/- 3.45%, p < 0.001; LAMB2: 6.86 +/- 3.46%, 38.54 +/- 4.13%, p < 0.001). The most enriched canonical pathways in PC included glycoprotein-6 signaling and mammalian target of rapamycin (mTOR). CONCLUSION: We identified key proteins differentially expressed between PC and PA using proteomic analyses of parathyroid neoplasms. These findings may help to diagnose PC accurately and elucidate potential therapeutic targets.
ESTHER : Kong_2023_Eur.J.Endocrinol__
PubMedSearch : Kong_2023_Eur.J.Endocrinol__
PubMedID: 36995894
Gene_locus related to this paper: human-CIB

Title : Rapid biosensor development using plant hormone receptors as reprogrammable scaffolds - Beltran_2022_Nat.Biotechnol__
Author(s) : Beltran J , Steiner PJ , Bedewitz M , Wei S , Peterson FC , Li Z , Hughes BE , Hartley Z , Robertson NR , Medina-Cucurella AV , Baumer ZT , Leonard AC , Park SY , Volkman BF , Nusinow DA , Zhong W , Wheeldon I , Cutler SR , Whitehead TA
Ref : Nat Biotechnol , : , 2022
Abstract : A general method to generate biosensors for user-defined molecules could provide detection tools for a wide range of biological applications. Here, we describe an approach for the rapid engineering of biosensors using PYR1 (Pyrabactin Resistance 1), a plant abscisic acid (ABA) receptor with a malleable ligand-binding pocket and a requirement for ligand-induced heterodimerization, which facilitates the construction of sense-response functions. We applied this platform to evolve 21 sensors with nanomolar to micromolar sensitivities for a range of small molecules, including structurally diverse natural and synthetic cannabinoids and several organophosphates. X-ray crystallography analysis revealed the mechanistic basis for new ligand recognition by an evolved cannabinoid receptor. We demonstrate that PYR1-derived receptors are readily ported to various ligand-responsive outputs, including enzyme-linked immunosorbent assay (ELISA)-like assays, luminescence by protein-fragment complementation and transcriptional circuits, all with picomolar to nanomolar sensitivity. PYR1 provides a scaffold for rapidly evolving new biosensors for diverse sense-response applications.
ESTHER : Beltran_2022_Nat.Biotechnol__
PubMedSearch : Beltran_2022_Nat.Biotechnol__
PubMedID: 35726092

Title : Crystal Structures of the Plant Phospholipase A1 Proteins Reveal a Unique Dimerization Domain - Heo_2022_Molecules_27_2317
Author(s) : Heo Y , Lee I , Moon S , Yun JH , Kim EY , Park SY , Park JH , Kim WT , Lee W
Ref : Molecules , 27 : , 2022
Abstract : Phospholipase is an enzyme that hydrolyzes various phospholipid substrates at specific ester bonds and plays important roles such as membrane remodeling, as digestive enzymes, and the regulation of cellular mechanism. Phospholipase proteins are divided into following the four major groups according to the ester bonds they cleave off: phospholipase A1 (PLA1), phospholipase A2 (PLA2), phospholipase C (PLC), and phospholipase D (PLD). Among the four phospholipase groups, PLA1 has been less studied than the other phospholipases. Here, we report the first molecular structures of plant PLA1s: AtDSEL and CaPLA1 derived from Arabidopsis thaliana and Capsicum annuum, respectively. AtDSEL and CaPLA1 are novel PLA1s in that they form homodimers since PLAs are generally in the form of a monomer. The dimerization domain at the C-terminal of the AtDSEL and CaPLA1 makes hydrophobic interactions between each monomer, respectively. The C-terminal domain is also present in PLA1s of other plants, but not in PLAs of mammals and fungi. An activity assay of AtDSEL toward various lipid substrates demonstrates that AtDSEL is specialized for the cleavage of sn-1 acyl chains. This report reveals a new domain that exists only in plant PLA1s and suggests that the domain is essential for homodimerization.
ESTHER : Heo_2022_Molecules_27_2317
PubMedSearch : Heo_2022_Molecules_27_2317
PubMedID: 35408716
Gene_locus related to this paper: capan-a5yw95 , arath-At4g18550

Title : The Aqueous Extract of Humulus japonicus Ameliorates Cognitive Dysfunction in Alzheimer's Disease Models via Modulating the Cholinergic System - Kang_2022_J.Med.Food__
Author(s) : Kang CM , Bang JS , Park SY , Jung TW , Kim HC , Chung YH , Jeong JH
Ref : J Med Food , : , 2022
Abstract : Humulus japonicus (HJ) is an herbal medicine, which has been reported as being antioxidative and anti-inflammatory. The present study aimed to investigate the effect of oral administration of HJ water extract (HJW) on cognitive function through the cholinergic system in Alzheimer's disease (AD) mouse models. Institute of Cancer Research mice injected with beta-amyloid (Abeta) (1-42) (i.c.v.) and APP/PS1 transgenic (TG) mice were orally administered with HJW at 500 mg/kg/day for 3 weeks. Abeta-injected mice and APP/PS1 TG mice showed cognitive dysfunction, which was evaluated by various behavioral tests. HJW treatment significantly attenuated memory impairments in Abeta-injected mice and APP/PS1 TG mice. Abeta injection decreased acetylcholine (ACh) concentrations and choline acetyltransferase (ChAT) activity, and increased acetylcholinesterase (AChE) activity. These cholinergic impairments were also found in APP/PS1 TG mice. HJW significantly attenuated cholinergic alterations in Abeta-injected mice and TG mice. In addition, HJW significantly decreased Abeta plaque deposition in the cerebral cortex and hippocampus of TG mice. Therefore, the present study demonstrated that HJW protected against AD-related memory impairments via enhancing the cholinergic system and inhibiting Abeta plaque deposition.
ESTHER : Kang_2022_J.Med.Food__
PubMedSearch : Kang_2022_J.Med.Food__
PubMedID: 36178947

Title : Gemigliptin Alleviates Succinate-Induced Hepatic Stellate Cell Activation by Ameliorating Mitochondrial Dysfunction - Nguyen_2022_Endocrinol.Metab.(Seoul)__
Author(s) : Nguyen G , Park SY , Do DV , Choi DH , Cho EH
Ref : Endocrinol Metab (Seoul) , : , 2022
Abstract : BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4Is) are used clinically as oral antidiabetic agents. Although DPP-4Is are known to ameliorate liver fibrosis, the protective mechanism of DPP-4Is in liver fibrosis remains obscure. In this study, gemigliptin was used to investigate the potential of DPP-4Is to alleviate the progression of liver fibrosis. METHODS: To clarify the effects and mechanisms of gemigliptin, we conducted various experiments in LX-2 cells (immortalized human hepatic stellate cells [HSCs], the principal effectors of hepatic fibrogenesis), which were activated by succinate and exhibited elevated expression of -smooth muscle actin, collagen type 1, and pro-inflammatory cytokines and increased cell proliferation. In vivo, we examined the effects and mechanisms of gemigliptin on a high-fat, high-cholesterol-induced mouse model of nonalcoholic steatohepatitis (NASH). RESULTS: Gemigliptin decreased the expression of fibrogenesis markers and reduced the abnormal proliferation of HSCs. In addition, gemigliptin reduced the succinate-induced production of mitochondrial reactive oxygen species (ROS), intracellular ROS, and mitochondrial fission in HSCs. Furthermore, in the mouse model of NASH-induced liver fibrosis, gemigliptin alleviated both liver fibrosis and mitochondrial dysfunction. CONCLUSION: Gemigliptin protected against HSC activation and liver fibrosis by alleviating mitochondrial dysfunction and ROS production, indicating its potential as a strategy for preventing the development of liver disease.
ESTHER : Nguyen_2022_Endocrinol.Metab.(Seoul)__
PubMedSearch : Nguyen_2022_Endocrinol.Metab.(Seoul)__
PubMedID: 36377343

Title : Comparison of neuromuscular blockade recovery co-administered with neostigmine and different doses of calcium gluconate: a randomized control trial - Choi_2021_BMC.Anesthesiol_21_93
Author(s) : Choi SR , Kim JH , Lee KH , Park SY
Ref : BMC Anesthesiol , 21 :93 , 2021
Abstract : BACKGROUND: Calcium increases the probability of transmitter release at the neuromuscular junction. It is not known whether there is a dose-dependent relationship between the dosage of calcium gluconate and the probability of transmitter release for non-depolarizing neuromuscular blockade (NMB) recovery by acetylcholinesterase inhibitors (AchEIs). This study compared the neuromuscular recovery time and the incidence of postoperative residual curarization (PORC) according to the dosage of calcium gluconate co-administered with neostigmine in three patient groups. METHODS: Patients were randomly allocated to a control group, a 5 mg/kg calcium gluconate group (calcium 5 group), or a 10 mg/kg calcium gluconate group (calcium 10 group). In patients with a TOF ratio (TOFr) between 0.2-0.7, 0.04 mg/kg of neostigmine was administered and both 0.2 mg of glycopyrrolate and 0.4 mg of atropine per 1 mg of neostigmine were administered. And additional 5 or 10 mg/kg of calcium gluconate were administrated to the calcium 5 and 10 groups. The primary endpoint was neuromuscular recovery time (the time between reversal and TOFr<=0.9). The secondary endpoints were the incidence of PORC at 5, 10, and 20 min after reversal administration and the train-of-four ratio (TOFr) at each time point. RESULTS: The neuromuscular recovery time was 5.3 min in the control group, 3.9 min in the calcium 5 group, and 4.1 min in the calcium 10 group, respectively (P = 0.004). The incidence of PORC at 5 min after neostigmine administration was 12 in the control group, 4 in the calcium 5 group, and 4 in the calcium 10 group, respectively, with statistical significance (P = 0.014). CONCLUSIONS: The co-administration of calcium gluconate with neostigmine safely promoted early NMB recovery, and the neuromuscular recovery time of the calcium 10 group tended to be more evenly distributed than that of the calcium 5 group. TRIAL REGISTRATION: ). Date of registration: August 122,019.
ESTHER : Choi_2021_BMC.Anesthesiol_21_93
PubMedSearch : Choi_2021_BMC.Anesthesiol_21_93
PubMedID: 33781234

Title : In Vitro Metabolism of Donepezil in Liver Microsomes Using Non-Targeted Metabolomics - Kim_2021_Pharmaceutics_13_
Author(s) : Kim SE , Seo HJ , Jeong Y , Lee GM , Ji SB , Park SY , Wu Z , Lee S , Kim S , Liu KH
Ref : Pharmaceutics , 13 : , 2021
Abstract : Donepezil is a reversible acetylcholinesterase inhibitor that is currently the most commonly prescribed drug for the treatment of Alzheimer's disease. In general, donepezil is known as a safe and well-tolerated drug, and it was not associated with liver abnormalities in several clinical trials. However, rare cases of drug-related liver toxicity have been reported since it has become commercially available. Few studies have investigated the metabolic profile of donepezil, and the mechanism of liver damage caused by donepezil has not been elucidated. In this study, the in vitro metabolism of donepezil was investigated using liquid chromatography-tandem mass spectrometry based on a non-targeted metabolomics approach. To identify metabolites, the data were subjected to multivariate data analysis and molecular networking. A total of 21 donepezil metabolites (17 in human liver microsomes, 21 in mice liver microsomes, and 17 in rat liver microsomes) were detected including 14 newly identified metabolites. One potential reactive metabolite was identified in rat liver microsomal incubation samples. Metabolites were formed through four major metabolic pathways: (1) O-demethylation, (2) hydroxylation, (3) N-oxidation, and (4) N-debenzylation. This study indicates that a non-targeted metabolomics approach combined with molecular networking is a reliable tool to identify and detect unknown drug metabolites.
ESTHER : Kim_2021_Pharmaceutics_13_
PubMedSearch : Kim_2021_Pharmaceutics_13_
PubMedID: 34201744

Title : Cognitive-enhancing and ameliorative effects of acanthoside B in a scopolamine-induced amnesic mouse model through regulation of oxidative\/inflammatory\/cholinergic systems and activation of the TrkB\/CREB\/BDNF pathway - Karthivashan_2019_Food.Chem.Toxicol_129_444
Author(s) : Karthivashan G , Kweon MH , Park SY , Kim JS , Kim DH , Ganesan P , Choi DK
Ref : Food & Chemical Toxicology , 129 :444 , 2019
Abstract : Recently, our research team reported the anti-amnesic potential of desalted-hydroethanolic extracts of Salicornia europaea L. (SE-EE). In this study, we performed bioactivity-guided isolation and identification of Acanthoside B (Aca.B), from SE-EE, as the potential bioactive candidate and examined anti-amnesic activity with its potential mechanism of action using an in vivo model. S7-L3-3 purified from SE-EE showed enhanced in vitro acetylcholinesterase (AChE) inhibitory activity. The isolated S7-L3-3 was identified and characterized as Aca.B using varied spectral analyses, i.e., Nuclear magnetic resonance (NMR), Ultraviolet-visible (UV-Vis), and Electrospray ionization-mass spectrometry (ESI-MS). In the in vitro studies, Aca.B exhibited negligible toxicity and showed a dose-dependent nitric oxide inhibitory potential in Lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. In the in vivo studies, the oral administration of Aca.B to mice showed enhanced bioavailability and dose-dependent repression of the behavioral/cognitive impairment by regulating the cholinergic function, restoring the antioxidant status, attenuating the inflammatory cytokines/mediators and actively enriching neurotropic proteins in the hippocampal regions of the scopolamine-administered mice.
ESTHER : Karthivashan_2019_Food.Chem.Toxicol_129_444
PubMedSearch : Karthivashan_2019_Food.Chem.Toxicol_129_444
PubMedID: 31077737

Title : Therapeutic strategies and nano-drug delivery applications in management of ageing Alzheimer's disease - Karthivashan_2018_Drug.Deliv_25_307
Author(s) : Karthivashan G , Ganesan P , Park SY , Kim JS , Choi DK
Ref : Drug Deliv , 25 :307 , 2018
Abstract : In recent years, the incidental rate of neurodegenerative disorders has increased proportionately with the aging population. Alzheimer's disease (AD) is one of the most commonly reported neurodegenerative disorders, and it is estimated to increase by roughly 30% among the aged population. In spite of screening numerous drug candidates against various molecular targets of AD, only a few candidates - such as acetylcholinesterase inhibitors are currently utilized as an effective clinical therapy. However, targeted drug delivery of these drugs to the central nervous system (CNS) exhibits several limitations including meager solubility, low bioavailability, and reduced efficiency due to the impediments of the blood-brain barrier (BBB). Current advances in nanotechnology present opportunities to overcome such limitations in delivering active drug candidates. Nanodrug delivery systems are promising in targeting several therapeutic moieties by easing the penetration of drug molecules across the CNS and improving their bioavailability. Recently, a wide range of nano-carriers, such as polymers, emulsions, lipo-carriers, solid lipid carriers, carbon nanotubes, metal based carriers etc., have been adapted to develop successful therapeutics with sustained release and improved efficacy. Here, we discuss few recently updated nano-drug delivery applications that have been adapted in the field of AD therapeutics, and future prospects on potential molecular targets for nano-drug delivery systems.
ESTHER : Karthivashan_2018_Drug.Deliv_25_307
PubMedSearch : Karthivashan_2018_Drug.Deliv_25_307
PubMedID: 29350055

Title : Comparative Studies on Behavioral, Cognitive and Biomolecular Profiling of ICR, C57BL\/6 and Its Sub-Strains Suitable for Scopolamine-Induced Amnesic Models - Karthivashan_2017_Int.J.Mol.Sci_18_
Author(s) : Karthivashan G , Park SY , Kim JS , Cho DY , Ganesan P , Choi DK
Ref : Int J Mol Sci , 18 : , 2017
Abstract : Cognitive impairment and behavioral disparities are the distinctive baseline features to investigate in most animal models of neurodegenerative disease. However, neuronal complications are multifactorial and demand a suitable animal model to investigate their underlying basal mechanisms. By contrast, the numerous existing neurodegenerative studies have utilized various animal strains, leading to factual disparity. Choosing an optimal mouse strain for preliminary assessment of neuronal complications is therefore imperative. In this study, we systematically compared the behavioral, cognitive, cholinergic, and inflammatory impairments of outbred ICR and inbred C57BL/6 mice strains subject to scopolamine-induced amnesia. We then extended this study to the sub-strains C57BL/6N and C57BL/6J, where in addition to the above-mentioned parameters, their endogenous antioxidant levels and cAMP response-element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) protein expression were also evaluated. Compared with the ICR strain, the scopolamine-inflicted C57BL/6 strains exhibited a substantial reduction of spontaneous alternation and an approximately two-fold increase in inflammatory protein expression, compared to the control group. Among the sub-strains, scopolamine-treated C57BL/6N strains exhibited declined step-through latency, elevated acetylcholinesterase (AChE) activity and inflammatory protein expression, associated with reduced endogenous antioxidant levels and p-CREB/BDNF expression, compared to the control and tacrine-treated groups. This indicates that the C57BL/6N strains exhibit significantly enhanced scopolamine-induced neuronal impairment compared to the other evaluated strains.
ESTHER : Karthivashan_2017_Int.J.Mol.Sci_18_
PubMedSearch : Karthivashan_2017_Int.J.Mol.Sci_18_
PubMedID: 28792471

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 : Incidence and Prevalence of Myasthenia Gravis in Korea: A Population-Based Study Using the National Health Insurance Claims Database - Park_2016_J.Clin.Neurol_12_340
Author(s) : Park SY , Lee JY , Lim NG , Hong YH
Ref : J Clin Neurol , 12 :340 , 2016
Abstract : BACKGROUND AND PURPOSE: There have been a few national population-based epidemiological studies of myasthenia gravis (MG) with wide variation of incidence and prevalence rates worldwide. Herein we report the first nationwide population-based epidemiological study of MG in Korea.
METHODS: We attempted to estimate the incidence and prevalence rates of MG using the Korean National Health Insurance claims database for 2010 to 2013. Cases with MG were defined as those having claim records with a principal diagnosis of MG and the prescription of acetylcholinesterase inhibitors or immunosuppressive agents including corticosteroids and azathioprine within 2 years after the diagnosis. The year 2010 was set as a washout period, such that patients were defined as incident cases if their first records of MG were observed in 2011.
RESULTS: In 2011 there were 1,236 incident cases, and the standardized incidence rate was 2.44 per 100,000 person-years. The standardized prevalence rates were 9.67 and 10.66 per 100,000 persons in 2010 and 2011, respectively. The incidence and prevalence rates peaked in the elderly population aged 60 to 69 years for both sexes.
CONCLUSIONS: This is one of the largest national population-based epidemiological studies of MG, and it has confirmed the high incidence and prevalence rates of MG in the elderly population of South Korea.
ESTHER : Park_2016_J.Clin.Neurol_12_340
PubMedSearch : Park_2016_J.Clin.Neurol_12_340
PubMedID: 27165426

Title : Is Lipase Supplementation before a High Fat Meal Helpful to Patients with Functional Dyspepsia? -
Author(s) : Park SY , Rew JS
Ref : Gut Liver , 9 :433 , 2015
PubMedID: 26087858

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 : Draft Genome Sequence of Cladonia macilenta KoLRI003786, a Lichen-Forming Fungus Producing Biruloquinone - Park_2013_Genome.Announc_1_e00695
Author(s) : Park SY , Choi J , Kim JA , Jeong MH , Kim S , Lee YH , Hur JS
Ref : Genome Announc , 1 : , 2013
Abstract : The lichen-forming fungus Cladonia macilenta strain KoLRI003786 is capable of producing an acetylcholinesterase inhibitor, biruloquinone, which effectively prevents neurodegeneration in Alzheimer's disease. Laying the foundation to unravel the biruloquinone biosynthetic pathway, we present the 37.11-Mb draft genome sequence of strain KoLRI003786.
ESTHER : Park_2013_Genome.Announc_1_e00695
PubMedSearch : Park_2013_Genome.Announc_1_e00695
PubMedID: 24009123

Title : Optimization of culture conditions for production of a novel cold-active lipase from Pichia lynferdii NRRL Y-7723 - Park_2013_J.Agric.Food.Chem_61_882
Author(s) : Park SY , Kim JY , Bae JH , Hou CT , Kim HR
Ref : Journal of Agricultural and Food Chemistry , 61 :882 , 2013
Abstract : Lipases with abnormal properties such as thermostability, alkalinity, acidity, and cold activity receive industrial attention because of their usability under restricted reaction conditions. Most microbial cold-active lipases originate from psychrotrophic and psychrophilic microorganisms found in Antarctic regions, which has led to difficulties in the practical production of cold-active lipase. Recently, a mesophilic yeast, Pichia lynferdii NRRL Y-7723, was reported to produce a novel cold-active lipase. This study focused on optimization of environmental factors, while giving particular attention to the relationships between given factors and incubation time, to maximize the production of a novel cold-active lipase from P. lynferdii NRRL Y-7723. Maximum lipase production was highly dependent on the incubation time at a given environmental factor. Lipase production varied with incubation time at a given temperature, and 20 degrees C was selected as the optimum temperature for lipase production. Fructose was selected as the best carbon source, and maximum lipase production was obtained when it was present at 0.7% (w/v). Yeast extract was an efficient organic nitrogen source, with maximum lipase production occurring at 0.9% (w/v). Specifically, at the optimum yeast extract level the lipase production was >10 times higher than the productivity under standard conditions. All natural oils tested showed lipase production, but their maximum productivities varied according to incubation time and oil species.
ESTHER : Park_2013_J.Agric.Food.Chem_61_882
PubMedSearch : Park_2013_J.Agric.Food.Chem_61_882
PubMedID: 23305314

Title : Sulforaphane induced adipolysis via hormone sensitive lipase activation, regulated by AMPK signaling pathway - Lee_2012_Biochem.Biophys.Res.Commun_426_492
Author(s) : Lee JH , Moon MH , Jeong JK , Park YG , Lee YJ , Seol JW , Park SY
Ref : Biochemical & Biophysical Research Communications , 426 :492 , 2012
Abstract : Sulforaphane, an aliphatic isothiocyanate derived from cruciferous vegetables, is known for its antidiabetic properties. The effects of sulforaphane on lipid metabolism in adipocytes are not clearly understood. Here, we investigated whether sulforaphane stimulates lipolysis. Mature adipocytes were incubated with sulforaphane for 24h and analyzed using a lipolysis assay which quantified glycerol released into the medium. We investigated gene expression of hormone-sensitive lipase (HSL), and levels of HSL phosphorylation and AMP-activated protein kinase on sulforaphane-mediated lipolysis in adipocytes. Sulforaphane promoted lipolysis and increased both HSL gene expression and HSL activation. Sulforaphane suppressed AMPK phosphorylation at Thr-172 in a dose-dependent manner, which was associated with a decrease in HSL phosphorylation at Ser-565, enhancing the phosphorylation of HSL Ser-563. Taken together, these results suggest that sulforaphane promotes lipolysis via hormone sensitive lipase activation mediated by decreasing AMPK signal activation in adipocytes.
ESTHER : Lee_2012_Biochem.Biophys.Res.Commun_426_492
PubMedSearch : Lee_2012_Biochem.Biophys.Res.Commun_426_492
PubMedID: 22982310

Title : Terpenoids as potential anti-Alzheimer's disease therapeutics - Yoo_2012_Molecules_17_3524
Author(s) : Yoo KY , Park SY
Ref : Molecules , 17 :3524 , 2012
Abstract : Alzheimer's disease (AD) is one of the most well-known neurodegenerative diseases and explains 50-60% of dementia in patients. The prevalence rate of AD is positively correlated with age and AD affects >/= 40% of those over 85 years old. The major AD therapeutics available on the market are acetylcholinesterase inhibitors, such as tacrine and donepezil. New therapeutic agents that can block the disease-inducing mechanisms are essential. Diverse efforts have been made to discover anti-AD agents from natural sources. In this review article, we describe some representative terpenoids such as ginsenosides, gingkolides, and canabinoids as potential anti-AD agents. These compounds exhibit promising in vitro and in vivo biological activities, but are still waiting clinical trials. Additionally, we also discuss some terpenoids including cornel iridoid glycoside, oleanolic acid, tenuifolin, cryptotanshinone, and ursolic acid, which are under investigation for their in vitro and in vivo animal studies.
ESTHER : Yoo_2012_Molecules_17_3524
PubMedSearch : Yoo_2012_Molecules_17_3524
PubMedID: 22430119

Title : Screening and identification of a novel esterase EstPE from a metagenomic DNA library - Park_2011_J.Microbiol_49_7
Author(s) : Park SY , Shin HJ , Kim GJ
Ref : J Microbiol , 49 :7 , 2011
Abstract : Esterases represent a large family of hydrolases with broad substrate specificity and functional sequence space. Although many attempts to screen new esterases have been conducted, there have been few reports conducted to discriminate unique enzymes from typical ones based on novel structure and function. In this study, we discovered an esterase and a novel family through a successive assay of whole cells and crude lysates (oxidative open condition). The screened putative esterases from the metagenomic DNA of salted shrimp consisted of 753 bp encoding 27 kDa of polypeptide, namely PE esterase. Sequence analyses revealed that an identical gene was reported from whole genome sequencing of Stenotrophomonas maltophilia K279a. However, its biochemical and phylogenetic characteristics have not yet been evaluated. PE esterase was overexpressed only by the MBP fusion state in E. coli and was easily purified using an affinity column. This enzyme showed a typical spectrum of substrate specificity and possessed the consensus motifs, Ser-Asp-His and GXSXG, which are essential for most esterase/lipase superfamilies. Interestingly, the entire organization of the ORF and consensus sequence around the active site were distinct from the related enzymes, and its structure could be affected by a reducing agent, DTT.
ESTHER : Park_2011_J.Microbiol_49_7
PubMedSearch : Park_2011_J.Microbiol_49_7
PubMedID: 21369973

Title : Potential therapeutic agents against Alzheimer's disease from natural sources - Park_2010_Arch.Pharm.Res_33_1589
Author(s) : Park SY
Ref : Arch Pharm Res , 33 :1589 , 2010
Abstract : The average human life span in developed countries has increased to more than 80 years following rapid breakthrough and developments in modern medicine and science, resulting in prolonged life expectancy and increase in the population counts of the geriatric age group. This translates into a dramatic increase in disease burden of elderly patients suffering from senile disorders including neurodegenerative diseases, particularly Alzheimer's disease (AD). AD is characterized by the death of nerve cells in the cerebral cortex and is the most common subtype of dementia that affected 25 million people worldwide in 2000 and is expected to increase to 114 million by 2050. Despite the exponential growth in the number of AD patients, only acetylcholinesterase (AChE) inhibitors are being currently used to treat AD. It is well known that AChE inhibitors can alleviate the symptoms of AD but not halt the disease progression. Consequently, therapeutic agents against AD acting at various pathologic levels are needed. In the recent decade, natural products with anti-AD properties have attracted much attention. But very few natural products have been investigated in a scientifically justifiable method for these biological activities. Following a detailed research process, it is certain that natural products have a strong potential to develop biologically active compounds with new chemical structures. Many studies have been carried out to identify the naturally occurring anti-AD agents. This review article describes the molecular targets aiming at developing the anti-AD agents including the inhibition of AChE, inhibition of Abeta production by enhancing alpha-secretase (non-amyloidogenic pathway) or inhibiting beta- and gamma-secretases (amyloidogenic pathway), alleviating Abeta-induced neurotoxicity or reducing Abeta-induced neuroinflammation. In addition, this paper summarizes the potential of some of the natural products that might inhibit specific molecular targets and slow the progression of this disease.
ESTHER : Park_2010_Arch.Pharm.Res_33_1589
PubMedSearch : Park_2010_Arch.Pharm.Res_33_1589
PubMedID: 21052936

Title : Genome sequence of the polymyxin-producing plant-probiotic rhizobacterium Paenibacillus polymyxa E681 - Kim_2010_J.Bacteriol_192_6103
Author(s) : Kim JF , Jeong H , Park SY , Kim SB , Park YK , Choi SK , Ryu CM , Hur CG , Ghim SY , Oh TK , Kim JJ , Park CS , Park SH
Ref : Journal of Bacteriology , 192 :6103 , 2010
Abstract : Paenibacillus polymyxa E681, a spore-forming, low-G+C, Gram-positive bacterium isolated from the rhizosphere of winter barley grown in South Korea, has great potential for agricultural applications due to its ability to promote plant growth and suppress plant diseases. Here we present the complete genome sequence of P. polymyxa E681. Its 5.4-Mb genome encodes functions specialized to the plant-associated lifestyle and characteristics that are beneficial to plants, such as the production of a plant growth hormone, antibiotics, and hydrolytic enzymes.
ESTHER : Kim_2010_J.Bacteriol_192_6103
PubMedSearch : Kim_2010_J.Bacteriol_192_6103
PubMedID: 20851896
Gene_locus related to this paper: paep6-e0ra24 , paep6-e0rkv6 , paep6-e0rmc7 , paep6-e0rmu8 , paeps-e3ebx3

Title : Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium - Ma_2010_Nature_464_367
Author(s) : Ma LJ , van der Does HC , Borkovich KA , Coleman JJ , Daboussi MJ , Di Pietro A , Dufresne M , Freitag M , Grabherr M , Henrissat B , Houterman PM , Kang S , Shim WB , Woloshuk C , Xie X , Xu JR , Antoniw J , Baker SE , Bluhm BH , Breakspear A , Brown DW , Butchko RA , Chapman S , Coulson R , Coutinho PM , Danchin EG , Diener A , Gale LR , Gardiner DM , Goff S , Hammond-Kosack KE , Hilburn K , Hua-Van A , Jonkers W , Kazan K , Kodira CD , Koehrsen M , Kumar L , Lee YH , Li L , Manners JM , Miranda-Saavedra D , Mukherjee M , Park G , Park J , Park SY , Proctor RH , Regev A , Ruiz-Roldan MC , Sain D , Sakthikumar S , Sykes S , Schwartz DC , Turgeon BG , Wapinski I , Yoder O , Young S , Zeng Q , Zhou S , Galagan J , Cuomo CA , Kistler HC , Rep M
Ref : Nature , 464 :367 , 2010
Abstract : Fusarium species are among the most important phytopathogenic and toxigenic fungi. To understand the molecular underpinnings of pathogenicity in the genus Fusarium, we compared the genomes of three phenotypically diverse species: Fusarium graminearum, Fusarium verticillioides and Fusarium oxysporum f. sp. lycopersici. Our analysis revealed lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes and account for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity, indicative of horizontal acquisition. Experimentally, we demonstrate the transfer of two LS chromosomes between strains of F. oxysporum, converting a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in F. oxysporum. These findings put the evolution of fungal pathogenicity into a new perspective.
ESTHER : Ma_2010_Nature_464_367
PubMedSearch : Ma_2010_Nature_464_367
PubMedID: 20237561
Gene_locus related to this paper: fusox-a0a1d3s5h0 , gibf5-fus2 , fusof-f9f2k2 , fusof-f9f3l6 , fusof-f9f6t8 , fusof-f9f6v2 , fusof-f9f132 , fusof-f9f781 , fusof-f9fd72 , fusof-f9fd90 , fusof-f9fem0 , fusof-f9fhk2 , fusof-f9fj19 , fusof-f9fj20 , fusof-f9fki8 , fusof-f9fmx2 , fusof-f9fnt4 , fusof-f9fpy4 , fusof-f9fvs6 , fusof-f9fwu0 , fusof-f9fxz4 , fusof-f9fzy5 , fusof-f9g2a2 , fusof-f9g3b1 , fusof-f9g5h7 , fusof-f9g6e6 , fusof-f9g6y7 , fusof-f9g7b0 , fusof-f9g797 , fusof-f9g972 , fusof-f9ga50 , fusof-f9gck4 , fusof-f9gd15 , gibze-a8w610 , gibze-b1pdn0 , gibze-i1r9e6 , gibze-i1rda9 , gibze-i1rdk7 , gibze-i1rec8 , gibze-i1rgs0 , gibze-i1rgy0 , gibze-i1rh52 , gibze-i1rhi8 , gibze-i1rig9 , gibze-i1rip5 , gibze-i1rpg6 , gibze-i1rsg2 , gibze-i1rv36 , gibze-i1rxm5 , gibze-i1rxp8 , gibze-i1rxv5 , gibze-i1s1u3 , gibze-i1s3j9 , gibze-i1s6l7 , gibze-i1s8i8 , gibze-i1s9x4 , gibze-q4huy1 , gibze-i1rg17 , fuso4-j9mvr9 , fuso4-j9ngs6 , fuso4-j9niq8 , fuso4-j9nqm2 , gibze-i1rb76 , gibze-i1s1m7 , gibze-i1s3z6 , gibze-i1rd78 , gibze-i1rgl9 , gibze-i1rjp7 , gibze-i1s1q6 , gibze-i1ri35 , gibze-i1rf76 , gibze-i1rhp3 , fusc1-n4uj11 , fusc4-n1s9p6 , gibf5-s0dqr2 , gibm7-w7n1b5 , fusof-f9g6q0 , gibm7-w7n497 , fusox-x0bme4 , gibm7-w7mcf8 , gibm7-w7mak5 , fusox-x0a2c5 , gibm7-w7mum7 , fusox-w9iyc7 , gibm7-w7maw6 , gibm7-w7msi0 , gibm7-w7luf0 , gibm7-w7msa3 , gibm7-w7mna8 , gibm7-w7n8b7 , gibm7-w7n564 , fusox-w9jpi0 , gibm7-w7ngc3 , gibm7-w7m4v6 , gibm7-w7m4v2 , gibm7-w7lt61 , gibm7-w7mly6 , gibm7-w7ncn3 , fusox-w9ibd7 , fusof-f9fnm6 , gibm7-w7n526 , gibza-a0a016pda4 , gibza-a0a016pl96 , gibm7-w7muq1 , fusof-f9gfd3 , gibm7-w7mt52 , gibze-i1rjb5 , gibf5-s0ehu3 , fusox-w9hvf0 , gibze-i1rkc4 , gibm7-w7mv30 , gibze-a0a1c3ylb1 , fuso4-a0a0c4diy4 , gibm7-w7n4n0 , gibze-gra11 , gibze-fsl2 , gibf5-fub4 , gibf5-fub5 , gibf5-fus5 , gibm7-dlh1

Title : Anti-amnesic effect of Chong-Myung-Tang on scopolamine-induced memory impairments in mice - Lee_2010_J.Ethnopharmacol_132_70
Author(s) : Lee MR , Yun BS , Park SY , Ly SY , Kim SN , Han BH , Sung CK
Ref : J Ethnopharmacol , 132 :70 , 2010
Abstract : AIM OF THE STUDY: Chong-Myung-Tang (CMT) consisted of Acorus gramineus Soland, Polygala tenuifolia Willdenow, and Poria cocos Wolf is one of the traditional Korean herbal medicines used for the therapy of learning and memory improvement. The present study was investigated the effect of CMT on learning and memory functions in SCOP-induced memory deficits mice. MATERIALS AND METHODS: The cognitive-enhancing effect of CMT on amnesic mice induced by SCOP was investigated by assessing the passive avoidance test and the Morris water maze test. In order to confirm the underlying mechanisms of memory enhancing effects of CMT, activities of AChE, choline acetyltransferase (ChAT), and antioxidant enzymes were measured. RESULTS: Administration of CMT significantly restored memory impairments induced by SCOP in the passive avoidance test and also reduced escape latency during trial sessions in the Morris water maze test. The increased AChE activity produced by SCOP was significantly inhibited by CMT. CMT significantly enhanced ChAT activity. Moreover, treatment with CMT to the amnesic mice induced by SCOP considerably decreased malondialdehyde levels and restored activities of superoxide dismutase and catalase to the control values. CONCLUSIONS: These results suggest that CMT may be useful for the cognitive improvement via regulation of cholinergic marker enzyme activities and the antioxidant defense system.
ESTHER : Lee_2010_J.Ethnopharmacol_132_70
PubMedSearch : Lee_2010_J.Ethnopharmacol_132_70
PubMedID: 20673844

Title : High-resolution structure of ybfF from Escherichia coli K12: a unique substrate-binding crevice generated by domain arrangement. - Park_2008_J.Mol.Biol_376_1426
Author(s) : Park SY , Lee SH , Lee J , Nishi K , Kim YS , Jung CH , Kim JS
Ref : Journal of Molecular Biology , 376 :1426 , 2008
Abstract : Esterases are one of the most common enzymes and are involved in diverse cellular functions. ybfF protein from Escherichia coli (Ec_ybfF) belongs to the esterase family for the large substrates, palmitoyl coenzyme A and malonyl coenzyme A, which are important cellular intermediates for energy conversion and biomolecular synthesis. To obtain molecular information on ybfF esterase, which is found in a wide range of microorganisms, we elucidated the crystal structures of Ec_ybfF in complexes with small molecules at resolutions of 1.1 and 1.68 A, respectively. The structure of Ec_ybfF is composed of a globular alpha/beta hydrolase domain with a three-helical bundle cap, which is linked by a kinked helix to the alpha/beta hydrolase domain. It contains a catalytic tetrad of Ser-His-Asp-Ser with the first Ser acting as a nucleophile. The unique spatial arrangement and orientation of the helical cap with respect to the alpha/beta hydrolase domain form a substrate-binding crevice for large substrates. The helical cap is also directly involved in catalysis by providing a substrate anchor, viz., the conserved residues of Arg123 and Tyr208. The high-resolution structure of Ec_ybfF shows that the inserted helical bundle structure and its spatial orientation with respect to the alpha/beta hydrolase domain are critical for creating a large inner space and constituting a specific active site, thereby providing the broad substrate spectrum toward large biomolecules.
ESTHER : Park_2008_J.Mol.Biol_376_1426
PubMedSearch : Park_2008_J.Mol.Biol_376_1426
PubMedID: 18215690
Gene_locus related to this paper: ecoli-ybff

Title : A new esterase showing similarity to putative dienelactone hydrolase from a strict marine bacterium, Vibrio sp. GMD509 - Park_2007_Appl.Microbiol.Biotechnol_77_107
Author(s) : Park SY , Kim JT , Kang SG , Woo JH , Lee JH , Choi HT , Kim SJ
Ref : Applied Microbiology & Biotechnology , 77 :107 , 2007
Abstract : Vibrio sp. GMD509, a marine bacterium isolated from eggs of the sea hare, exhibited lipolytic activity on tributyrin (TBN) plate, and the gene representing lipolytic activity was cloned. As a result, an open reading frame (ORF) consisting of 1,017 bp (338 aa) was found, and the deduced amino acid sequence of the ORF showed low similarity (< 20%) to alpha/beta hydrolases such as dienelactone hydrolases and esterase/lipase with G-X(1)-S-X(2)-G sequence conserved. Phylogenetic analysis suggested that the protein belonged to a new family of esterase/lipase together with various hypothetical proteins. The enzyme was overexpressed in Escherichia coli and purified to homogeneity. The purified enzyme (Vlip509) showed the best hydrolyzing activity toward p-nitrophenyl butyrate (C(4)) among various p-nitrophenyl esters (C(2) to C(18)), and optimal activity of Vlip509 occurred at 30 degrees C and pH 8.5, respectively. Kinetic parameters toward p-nitrophenyl butyrate were determined as K (m) (307 muM), k (cat) (5.72 s(-1)), and k (cat)/K (m) (18.61 s(-1) mM(-1)). Furthermore, Vlip509 preferentially hydrolyzed the S-enantiomer of racemic ofloxacin ester. Despite its sequence homology to dienelactone hydrolase, Vlip509 showed no dienelactone hydrolase activity. This study represents the identification of a novel lipolytic enzyme from marine environment.
ESTHER : Park_2007_Appl.Microbiol.Biotechnol_77_107
PubMedSearch : Park_2007_Appl.Microbiol.Biotechnol_77_107
PubMedID: 17712554
Gene_locus related to this paper: 9vibr-a8jy01

Title : Crystallization and preliminary X-ray diffraction analysis of ybfF, a new esterase from Escherichia coli K12 - Park_2007_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_63_1051
Author(s) : Park SY , Lee SH , Lee J , Jung CH , Kim JS
Ref : Acta Crystallographica Sect F Struct Biol Cryst Commun , 63 :1051 , 2007
Abstract : The product of the recently discovered ybfF gene, which belongs to the esterase family, does not show high sequence similarity to other esterases. To provide the molecular background to the enzymatic mechanism of the ybfF esterase, the ybfF protein from Escherichia coli K12 (Ec_ybfF) was cloned, expressed and purified. The Ec_ybfF protein was crystallized from 60% Tacsimate and 0.1 M bis-Tris propane buffer pH 7.0. Diffraction data were collected to 1.10 A resolution using synchrotron radiation. The crystal belongs to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 66.09, b = 90.71, c = 92.88 A. With two Ec_ybfF molecules in the asymmetric unit, the crystal volume per unit protein weight is 2.17 A(3) Da(-1), corresponding to a solvent content of 42%.
ESTHER : Park_2007_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_63_1051
PubMedSearch : Park_2007_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_63_1051
PubMedID: 18084091
Gene_locus related to this paper: ecoli-ybff

Title : New cold-adapted lipase from Photobacterium lipolyticum sp. nov. that is closely related to filamentous fungal lipases - Ryu_2006_Appl.Microbiol.Biotechnol_70_321
Author(s) : Ryu HS , Kim HK , Choi WC , Kim MH , Park SY , Han NS , Oh TK , Lee JK
Ref : Applied Microbiology & Biotechnology , 70 :321 , 2006
Abstract : A Photobacterium strain, M37, showing lipolytic activity, was previously isolated from an intertidal flat of the Yellow Sea in Korea and identified as Photobacterium lipolyticum sp. nov. In the present study, the corresponding gene was cloned using the shotgun method. The amino acid sequence deduced from the nucleotide sequence (1,023 bp) corresponded to a protein of 340 amino acid residues with a molecular weight of 38,026. No sequence similarity was found with any known bacterial lipases/esterases; instead, the most similar enzymes were several filamentous fungal lipases. Although the similarity was very low (less than 16%), there were many conserved regions over the entire sequence and N-terminal oxyanion hole (RG) region, a signature sequence of filamentous fungal lipases. The novel protein M37 was produced in both a soluble and insoluble form when the Escherichia coli cells harboring the gene were cultured at 18 degrees C. The soluble protein exhibited lipase activity in a pH-stat assay using an olive oil emulsion. The M37 lipase also displayed a maximum activity at 25 degrees C and maintained its activity at a low temperature range (5-25 degrees C) with an activation energy (E(a)) of 2.07 kcal/mol. Accordingly, these results indicate that the M37 lipase from P. lipolyticum sp. nov. is a new cold-adapted enzyme.
ESTHER : Ryu_2006_Appl.Microbiol.Biotechnol_70_321
PubMedSearch : Ryu_2006_Appl.Microbiol.Biotechnol_70_321
PubMedID: 16088345
Gene_locus related to this paper: 9gamm-q5drn8

Title : Hormone-sensitive lipase knockout mice have increased hepatic insulin sensitivity and are protected from short-term diet-induced insulin resistance in skeletal muscle and heart - Park_2005_Am.J.Physiol.Endocrinol.Metab_289_E30
Author(s) : Park SY , Kim HJ , Wang S , Higashimori T , Dong J , Kim YJ , Cline G , Li H , Prentki M , Shulman GI , Mitchell GA , Kim JK
Ref : American Journal of Physiology Endocrinol Metab , 289 :E30 , 2005
Abstract : Insulin resistance in skeletal muscle and heart plays a major role in the development of type 2 diabetes and diabetic heart failure and may be causally associated with altered lipid metabolism. Hormone-sensitive lipase (HSL) is a rate-determining enzyme in the hydrolysis of triglyceride in adipocytes, and HSL-deficient mice have reduced circulating fatty acids and are resistant to diet-induced obesity. To determine the metabolic role of HSL, we examined the changes in tissue-specific insulin action and glucose metabolism in vivo during hyperinsulinemic euglycemic clamps after 3 wk of high-fat or normal chow diet in awake, HSL-deficient (HSL-KO) mice. On normal diet, HSL-KO mice showed a twofold increase in hepatic insulin action but a 40% decrease in insulin-stimulated cardiac glucose uptake compared with wild-type littermates. High-fat feeding caused a similar increase in whole body fat mass in both groups of mice. Insulin-stimulated glucose uptake was reduced by 50-80% in skeletal muscle and heart of wild-type mice after high-fat feeding. In contrast, HSL-KO mice were protected from diet-induced insulin resistance in skeletal muscle and heart, and these effects were associated with reduced intramuscular triglyceride and fatty acyl-CoA levels in the fat-fed HSL-KO mice. Overall, these findings demonstrate the important role of HSL on skeletal muscle, heart, and liver glucose metabolism.
ESTHER : Park_2005_Am.J.Physiol.Endocrinol.Metab_289_E30
PubMedSearch : Park_2005_Am.J.Physiol.Endocrinol.Metab_289_E30
PubMedID: 15701680
Gene_locus related to this paper: mouse-hslip

Title : Cardiac-specific knock-out of lipoprotein lipase alters plasma lipoprotein triglyceride metabolism and cardiac gene expression - Augustus_2004_J.Biol.Chem_279_25050
Author(s) : Augustus A , Yagyu H , Haemmerle G , Bensadoun A , Vikramadithyan RK , Park SY , Kim JK , Zechner R , Goldberg IJ
Ref : Journal of Biological Chemistry , 279 :25050 , 2004
Abstract : Fatty acids are the primary energy source for the heart. The heart acquires fatty acids associated with albumin or derived from lipoprotein lipase (LpL)-mediated hydrolysis of lipoprotein triglyceride (TG). We generated heart-specific LpL knock-out mice (hLpL0) to determine whether cardiac LpL modulates the actions of peroxisome proliferator-activated receptors and affects whole body lipid metabolism. Male hLpL0 mice had significantly elevated plasma TG levels and decreased clearance of postprandial lipids despite normal postheparin plasma LpL activity. Very large density lipoprotein-TG uptake was decreased by 72% in hLpL0 hearts. However, heart uptake of albumin-bound free fatty acids was not altered. Northern blot analysis revealed a decrease in the expression of peroxisome proliferator-activated receptor alpha-response genes involved in fatty acid beta-oxidation. Surprisingly, the expression of glucose transporters 1 and 4 and insulin receptor substrate 2 was increased and that of pyruvate dehydrogenase kinase 4 and insulin receptor substrate 1 was reduced. Basal glucose uptake was increased markedly in hLpL0 hearts. Thus, the loss of LpL in the heart leads to defective plasma metabolism of TG. Moreover, fatty acids derived from lipoprotein TG and not just albumin-associated fatty acids are important for cardiac lipid metabolism and gene regulation.
ESTHER : Augustus_2004_J.Biol.Chem_279_25050
PubMedSearch : Augustus_2004_J.Biol.Chem_279_25050
PubMedID: 15028738

Title : Gene cloning and characterization of thermostable lipase from Bacillus stearothermophilus L1 - Kim_1998_Biosci.Biotechnol.Biochem_62_66
Author(s) : Kim HK , Park SY , Lee JK , Oh TK
Ref : Biosci Biotechnol Biochem , 62 :66 , 1998
Abstract : The gene coding for an extracellular lipase of Bacillus stearothermophilus L1 was cloned in Escherichia coli. Sequence analysis showed an open reading frame of 1254 bp, which encodes a polypeptide of 417 amino acid residues. The polypeptide was composed of a signal sequence (29 amino acids) and a mature protein of 388 amino acids. An alanine replaces the first glycine in the conserved pentapeptide (Gly-X-Ser-X-Gly) around the active site serine. The expressed lipase was purified by hydrophobic interaction and ion exchange chromatography using buffers containing 0.02% (v/v) Triton X-100. The lipase was most active at 60-65 degrees C and in alkaline conditions around pH 9-10. The lipase had highest activity toward p-nitrophenyl caprylate among the synthetic substrates and tripropionin among the triglycerides. It hydrolyzed beef tallow and palm oil more rapidly than olive oil at 50 degrees C.
ESTHER : Kim_1998_Biosci.Biotechnol.Biochem_62_66
PubMedSearch : Kim_1998_Biosci.Biotechnol.Biochem_62_66
PubMedID: 9501519
Gene_locus related to this paper: geost-lipas