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| | <StructureSection load='5i94' size='340' side='right'caption='[[5i94]], [[Resolution|resolution]] 2.98Å' scene=''> | | <StructureSection load='5i94' size='340' side='right'caption='[[5i94]], [[Resolution|resolution]] 2.98Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5i94]] 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=5I94 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I94 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5i94]] 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=5I94 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I94 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=69V:2-PHENYL-N-{5-[4-({5-[(PHENYLACETYL)AMINO]-1,3,4-THIADIAZOL-2-YL}OXY)PIPERIDIN-1-YL]-1,3,4-THIADIAZOL-2-YL}ACETAMIDE'>69V</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.983Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fi2|5fi2]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=69V:2-PHENYL-N-{5-[4-({5-[(PHENYLACETYL)AMINO]-1,3,4-THIADIAZOL-2-YL}OXY)PIPERIDIN-1-YL]-1,3,4-THIADIAZOL-2-YL}ACETAMIDE'>69V</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GLS, GLS1, KIAA0838 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5i94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i94 OCA], [https://pdbe.org/5i94 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i94 RCSB], [https://www.ebi.ac.uk/pdbsum/5i94 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i94 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutaminase Glutaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.2 3.5.1.2] </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=5i94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i94 OCA], [http://pdbe.org/5i94 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i94 RCSB], [http://www.ebi.ac.uk/pdbsum/5i94 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i94 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glutaminase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cerione, R]] | + | [[Category: Cerione R]] |
| - | [[Category: Huang, Q]] | + | [[Category: Huang Q]] |
| - | [[Category: Glutaminase c]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| 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 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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. Design and evaluation of novel glutaminase inhibitors. Bioorg Med Chem. 2016 Apr 15;24(8):1819-39. doi: 10.1016/j.bmc.2016.03.009. Epub , 2016 Mar 7. PMID:26988803 doi:http://dx.doi.org/10.1016/j.bmc.2016.03.009
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