5fi7: Difference between revisions
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<StructureSection load='5fi7' size='340' side='right' caption='[[5fi7]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='5fi7' size='340' side='right' caption='[[5fi7]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5fi7]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FI7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FI7 FirstGlance]. <br> | <table><tr><td colspan='2'>[[5fi7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FI7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FI7 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5XZ:2-PHENYL-~{N}-[5-[(3~{S})-3-[[5-(2-PHENYLETHANOYLAMINO)-1,3,4-THIADIAZOL-2-YL]OXY]PYRROLIDIN-1-YL]-1,3,4-THIADIAZOL-2-YL]ETHANAMIDE'>5XZ</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5XZ:2-PHENYL-~{N}-[5-[(3~{S})-3-[[5-(2-PHENYLETHANOYLAMINO)-1,3,4-THIADIAZOL-2-YL]OXY]PYRROLIDIN-1-YL]-1,3,4-THIADIAZOL-2-YL]ETHANAMIDE'>5XZ</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fi2|5fi2]], [[5fi6|5fi6]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fi2|5fi2]], [[5fi6|5fi6]]</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=5fi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fi7 OCA], [http://pdbe.org/5fi7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fi7 RCSB], [http://www.ebi.ac.uk/pdbsum/5fi7 PDBsum]</span></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=5fi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fi7 OCA], [http://pdbe.org/5fi7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fi7 RCSB], [http://www.ebi.ac.uk/pdbsum/5fi7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fi7 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Cerione, R]] | [[Category: Cerione, R]] | ||
[[Category: Huang, Q]] | [[Category: Huang, Q]] | ||
Revision as of 20:17, 15 November 2017
Crystal structure of human GAC in complex with inhibitor UPGL_00015: 2-phenyl-~{N}-[5-[(3~{S})-3-[[5-(2-phenylethanoylamino)-1,3,4-thiadiazol-2-yl]oxy]pyrrolidin-1-yl]-1,3,4-thiadiazol-2-yl]ethanamide
Structural highlights
Function[GLSK_HUMAN] Catalyzes the first reaction in the primary pathway for the renal catabolism of glutamine. Plays a role in maintaining acid-base homeostasis. Regulates the levels of the neurotransmitter glutamate in the brain. Isoform 2 lacks catalytic activity. Publication Abstract from PubMedA novel set of GAC (kidney glutaminase isoform C) inhibitors able to inhibit the enzymatic activity of GAC and the growth of the triple negative MDA-MB-231 breast cancer cells with low nanomolar potency is described. Compounds in this series have a reduced number of rotatable bonds, improved ClogPs, microsomal stability and ligand efficiency when compared to the leading GAC inhibitors BPTES and CB-839. Property improvements were achieved by the replacement of the flexible n-diethylthio or the n-butyl moiety present in the leading inhibitors by heteroatom substituted heterocycloalkanes. Design and evaluation of novel glutaminase inhibitors.,McDermott LA, Iyer P, Vernetti L, Rimer S, Sun J, Boby M, Yang T, Fioravanti M, O'Neill J, Wang L, Drakes D, Katt W, Huang Q, Cerione R Bioorg Med Chem. 2016 Apr 15;24(8):1819-39. doi: 10.1016/j.bmc.2016.03.009. Epub , 2016 Mar 7. PMID:26988803[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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