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6mhc
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6mhc is ON HOLD Authors: Petrunak, E.M., Stuckey, J.A. Description: Glutathione S-Transferase Omega 1 bound to covalent inhibitor 37 [[Category: Un...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Glutathione S-Transferase Omega 1 bound to covalent inhibitor 37== | |
| + | <StructureSection load='6mhc' size='340' side='right'caption='[[6mhc]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6mhc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MHC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MHC FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=JRM:methyl+N-(4-phenyl-1,3-thiazol-2-yl)-N-propanoylglycinate'>JRM</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6mhc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mhc OCA], [https://pdbe.org/6mhc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mhc RCSB], [https://www.ebi.ac.uk/pdbsum/6mhc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mhc ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/GSTO1_HUMAN GSTO1_HUMAN] Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities. Has S-(phenacyl)glutathione reductase activity. Has also glutathione S-transferase activity. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA) and dimethylarsonic acid.<ref>PMID:10783391</ref> <ref>PMID:11511179</ref> <ref>PMID:17226937</ref> <ref>PMID:18028863</ref> <ref>PMID:21106529</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Using reported glutathione S-transferase omega 1 (GSTO1-1) co-crystal structures, we designed and synthesized acrylamide-containing compounds that covalently bind to Cys32 on the catalytic site. Starting from a thiazole derivative 10 (GSTO1-1 IC50 = 0.6 microM), compound 18 was synthesized and co-crystalized with GSTO1. Modification on the amide moiety of hit compound 10 significantly increased the GSTO1-1 inhibitory potency. We solved the co-crystal structures of new derivatives, 37 and 44, bearing amide side chain bound to GSTO1. These new structures showed a reorientation of the phenyl thiazole core of inhibitors, 37 and 44, when compared to 18. Guided by the co-crystal structure of GSTO1:44, analog 49 was designed resulting in the most potent GSTO1-1 inhibitor (IC50 = 0.22 +/- 0.02 nM) known to date. We believe that our data will inform the future studies of developing GSTO1-1 as a new drug target for cancer therapy. | ||
| - | + | Structure-based Design of N-(5-phenylthiazol-2-yl)acrylamides as Novel and Potent Glutathione S-Transferase Omega 1 Inhibitors.,Dai W, Samanta S, Xue D, Petrunak EM, Stuckey JA, Han Y, Sun D, Wu Y, Neamati N J Med Chem. 2019 Feb 8. doi: 10.1021/acs.jmedchem.8b01960. PMID:30735370<ref>PMID:30735370</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Petrunak | + | <div class="pdbe-citations 6mhc" style="background-color:#fffaf0;"></div> |
| - | [[Category: Stuckey | + | |
| + | ==See Also== | ||
| + | *[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Petrunak EM]] | ||
| + | [[Category: Stuckey JA]] | ||
Current revision
Glutathione S-Transferase Omega 1 bound to covalent inhibitor 37
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