This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
6mhb
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Glutathione S-Transferase Omega 1 bound to covalent inhibitor 18== | |
| + | <StructureSection load='6mhb' size='340' side='right' caption='[[6mhb]], [[Resolution|resolution]] 2.75Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6mhb]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MHB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MHB FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JR7:N-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]propanamide'>JR7</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6mhb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mhb OCA], [http://pdbe.org/6mhb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mhb RCSB], [http://www.ebi.ac.uk/pdbsum/6mhb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mhb ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://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> | |
| - | + | </div> | |
| - | [[Category: Petrunak, E | + | <div class="pdbe-citations 6mhb" style="background-color:#fffaf0;"></div> |
| - | [[Category: Stuckey, J | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Petrunak, E M]] | ||
| + | [[Category: Stuckey, J A]] | ||
| + | [[Category: Transferase]] | ||
| + | [[Category: Transferase inhibitor]] | ||
| + | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 06:52, 21 February 2019
Glutathione S-Transferase Omega 1 bound to covalent inhibitor 18
| |||||||||||
