5fi7: Difference between revisions
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==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== | |||
<StructureSection load='5fi7' size='340' side='right'caption='[[5fi7]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5fi7]] is a 4 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=5FI7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FI7 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]] 2.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5fi7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fi7 OCA], [https://pdbe.org/5fi7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fi7 RCSB], [https://www.ebi.ac.uk/pdbsum/5fi7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fi7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GLSK_HUMAN 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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A 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<ref>PMID:26988803</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5fi7" style="background-color:#fffaf0;"></div> | ||
[[Category: Cerione | |||
==See Also== | |||
*[[Glutaminase 3D structures|Glutaminase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Cerione R]] | |||
[[Category: Huang Q]] | |||
Latest revision as of 09:52, 19 July 2023
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
FunctionGLSK_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. See AlsoReferences
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