Han Q

References (6)

Title : Crystal structure of acetylcholinesterase catalytic subunits of the malaria vector Anopheles gambiae - Han_2018_Insect.Sci_25_721
Author(s) : Han Q , Wong DM , Robinson H , Ding H , Lam PC , Totrov MM , Carlier PR , Li J
Ref : Insect Sci , 25 :721 , 2018
Abstract : Acetylcholinesterase (AChE) hydrolyzes the neurotransmitter acetylcholine at cholinergic synapses in the central nervous system (Toutant, 1989). Inhibition of the enzyme in insects could lead to the death of insects rapidly; thus AChE has been a molecular target for developing insecticides. This article is protected by copyright. All rights reserved.
ESTHER : Han_2018_Insect.Sci_25_721
PubMedSearch : Han_2018_Insect.Sci_25_721
PubMedID: 28247978
Gene_locus related to this paper: anoga-ACHE1

Title : 4H-Thieno[3,2-c]chromene based inhibitors of Notum Pectinacetylesterase - Han_2016_Bioorg.Med.Chem.Lett_26_1184
Author(s) : Han Q , Pabba PK , Barbosa J , Mabon R , Healy JP , Gardyan MW , Terranova KM , Brommage R , Thompson AY , Schmidt JM , Wilson AG , Xu X , Tarver JE, Jr. , Carson KG
Ref : Bioorganic & Medicinal Chemistry Lett , 26 :1184 , 2016
Abstract : A group of small molecule thienochromenes inhibitors of Notum Pectinacetylesterase are described. We developed SAR on three series based on carbon, oxygen and sulfur replacement of the 5-position. In each series, highly potent Notum Pectinacetylesterase inhibitors were identified.
ESTHER : Han_2016_Bioorg.Med.Chem.Lett_26_1184
PubMedSearch : Han_2016_Bioorg.Med.Chem.Lett_26_1184
PubMedID: 26821819

Title : Stimulation of cortical bone formation with thienopyrimidine based inhibitors of Notum Pectinacetylesterase - Tarver_2016_Bioorg.Med.Chem.Lett_26_1525
Author(s) : Tarver JE, Jr. , Pabba PK , Barbosa J , Han Q , Gardyan MW , Brommage R , Thompson AY , Schmidt JM , Wilson AG , He W , Lombardo VK , Carson KG , Wilson AGE
Ref : Bioorganic & Medicinal Chemistry Lett , 26 :1525 , 2016
Abstract : A group of small molecule thienopyrimidine inhibitors of Notum Pectinacetylesterase are described. We explored both 2-((5,6-thieno[2,3-d]pyrimidin-4-yl)thio)acetic acids and 2-((6,7-thieno[3,2-d]pyrimidin-4-yl)thio)acetic acids. In both series, highly potent, orally active Notum Pectinacetylesterase inhibitors were identified.
ESTHER : Tarver_2016_Bioorg.Med.Chem.Lett_26_1525
PubMedSearch : Tarver_2016_Bioorg.Med.Chem.Lett_26_1525
PubMedID: 26897593
Gene_locus related to this paper: human-NOTUM

Title : Biochemical identification and crystal structure of kynurenine formamidase from Drosophila melanogaster. - Han_2012_Biochem.J_446_253
Author(s) : Han Q , Robinson H , Li J
Ref : Biochemical Journal , 446 :253 , 2012
Abstract : KFase (kynurenine formamidase), also known as arylformamidase and formylkynurenine formamidase, efficiently catalyses the hydrolysis of NFK (N-formyl-L-kynurenine) to kynurenine. KFase is the second enzyme in the kynurenine pathway of tryptophan metabolism. A number of intermediates formed in the kynurenine pathway are biologically active and implicated in an assortment of medical conditions, including cancer, schizophrenia and neurodegenerative diseases. Consequently, enzymes involved in the kynurenine pathway have been considered potential regulatory targets. In the present study, we report, for the first time, the biochemical characterization and crystal structures of Drosophila melanogaster KFase conjugated with an inhibitor, PMSF. The protein architecture of KFase reveals that it belongs to the alpha/beta hydrolase fold family. The PMSF-binding information of the solved conjugated crystal structure was used to obtain a KFase and NFK complex using molecular docking. The complex is useful for understanding the catalytic mechanism of KFase. The present study provides a molecular basis for future efforts in maintaining or regulating kynurenine metabolism through the molecular and biochemical regulation of KFase.
ESTHER : Han_2012_Biochem.J_446_253
PubMedSearch : Han_2012_Biochem.J_446_253
PubMedID: 22690733
Gene_locus related to this paper: drome-CG9542

Title : Select small core structure carbamates exhibit high contact toxicity to carbamate-resistant strain malaria mosquitoes, Anopheles gambiae (Akron) - Wong_2012_PLoS.One_7_e46712
Author(s) : Wong DM , Li J , Chen QH , Han Q , Mutunga JM , Wysinski A , Anderson TD , Ding H , Carpenetti TL , Verma A , Islam R , Paulson SL , Lam PC , Totrov M , Bloomquist JR , Carlier PR
Ref : PLoS ONE , 7 :e46712 , 2012
Abstract : Acetylcholinesterase (AChE) is a proven target for control of the malaria mosquito (Anopheles gambiae). Unfortunately, a single amino acid mutation (G119S) in An. gambiae AChE-1 (AgAChE) confers resistance to the AChE inhibitors currently approved by the World Health Organization for indoor residual spraying. In this report, we describe several carbamate inhibitors that potently inhibit G119S AgAChE and that are contact-toxic to carbamate-resistant An. gambiae. PCR-RFLP analysis was used to confirm that carbamate-susceptible G3 and carbamate-resistant Akron strains of An. gambiae carry wild-type (WT) and G119S AChE, respectively. G119S AgAChE was expressed and purified for the first time, and was shown to have only 3% of the turnover number (k(cat)) of the WT enzyme. Twelve carbamates were then assayed for inhibition of these enzymes. High resistance ratios (>2,500-fold) were observed for carbamates bearing a benzene ring core, consistent with the carbamate-resistant phenotype of the G119S enzyme. Interestingly, resistance ratios for two oxime methylcarbamates, and for five pyrazol-4-yl methylcarbamates were found to be much lower (4- to 65-fold). The toxicities of these carbamates to live G3 and Akron strain An. gambiae were determined. As expected from the enzyme resistance ratios, carbamates bearing a benzene ring core showed low toxicity to Akron strain An. gambiae (LC(50)>5,000 mug/mL). However, one oxime methylcarbamate (aldicarb) and five pyrazol-4-yl methylcarbamates (4a-e) showed good to excellent toxicity to the Akron strain (LC(50) = 32-650 mug/mL). These results suggest that appropriately functionalized "small-core" carbamates could function as a resistance-breaking anticholinesterase insecticides against the malaria mosquito.
ESTHER : Wong_2012_PLoS.One_7_e46712
PubMedSearch : Wong_2012_PLoS.One_7_e46712
PubMedID: 23049714
Gene_locus related to this paper: anoga-ACHE1

Title : Chimeras of hepatic lipase and lipoprotein lipase. Domain localization of enzyme-specific properties - Davis_1992_J.Biol.Chem_267_21499
Author(s) : Davis RC , Wong H , Nikazy J , Wang K , Han Q , Schotz MC
Ref : Journal of Biological Chemistry , 267 :21499 , 1992
Abstract : Chimeric molecules between human lipoprotein lipase (LPL) and rat hepatic lipase (HL) were used to identify structural elements responsible for functional differences. Based on the close sequence homology with pancreatic lipase, both LPL and HL are believed to have a two-domain structure composed of an amino-terminal (NH2-terminal) domain containing the catalytic Ser-His-Asp triad and a smaller carboxyl-terminal (COOH-terminal) domain. Experiments with chimeric lipases containing the HL NH2-terminal domain and the LPL COOH-terminal domain (HL/LPL) or the reverse chimera (LPL/HL) showed that the NH2-terminal domain is responsible for the catalytic efficiency (Vmax/Km) of these enzymes. Furthermore, it was demonstrated that the stimulation of LPL activity by apolipoprotein C-II and the inhibition of activity by 1 M NaCl originate in structural features within the NH2-terminal domain. HL and LPL bind to vascular endothelium, presumably by interaction with cell surface heparan sulfate proteoglycans. However, the two enzymes differ significantly in their heparin affinity. Experiments with the chimeric lipases indicated that heparin binding avidity was primarily associated with the COOH-terminal domain. Specifically, both HL and the LPL/HL chimera were eluted from immobilized heparin by 0.75 M NaCl, whereas 1.1 M NaCl was required to elute LPL and the HL/LPL chimera. Finally, HL is more active than LPL in the hydrolysis of phospholipid substrates. However, the ratio of phospholipase to neutral lipase activity in both chimeric lipases was enhanced by the presence of the heterologous COOH-terminal domain, demonstrating that this domain strongly influences substrate specificity. The NH2-terminal domain thus controls the kinetic parameters of these lipases, whereas the COOH-terminal domain modulates substrate specificity and heparin binding.
ESTHER : Davis_1992_J.Biol.Chem_267_21499
PubMedSearch : Davis_1992_J.Biol.Chem_267_21499
PubMedID: 1400461