4ja8
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4ja8]] 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=4JA8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JA8 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4ja8]] 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=4JA8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JA8 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1K9:1-[5-(CYCLOPROPYLSULFAMOYL)-2-THIOPHEN-3-YL-PHENYL]-3-[3-(TRIFLUOROMETHYL)PHENYL]UREA'>1K9</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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]] 1.55Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1K9:1-[5-(CYCLOPROPYLSULFAMOYL)-2-THIOPHEN-3-YL-PHENYL]-3-[3-(TRIFLUOROMETHYL)PHENYL]UREA'>1K9</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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=4ja8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ja8 OCA], [https://pdbe.org/4ja8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ja8 RCSB], [https://www.ebi.ac.uk/pdbsum/4ja8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ja8 ProSAT]</span></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=4ja8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ja8 OCA], [https://pdbe.org/4ja8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ja8 RCSB], [https://www.ebi.ac.uk/pdbsum/4ja8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ja8 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/IDHP_HUMAN IDHP_HUMAN] Plays a role in intermediary metabolism and energy production. It may tightly associate or interact with the pyruvate dehydrogenase complex. | [https://www.uniprot.org/uniprot/IDHP_HUMAN IDHP_HUMAN] Plays a role in intermediary metabolism and energy production. It may tightly associate or interact with the pyruvate dehydrogenase complex. | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | A number of human cancers harbor somatic point mutations in the genes encoding isocitrate dehydrogenases- 1 and -2 (IDH1, IDH2). These mutations alter residues in the enzyme active sites and confer a gain-of-function in cancer cells, resulting in the accumulation and secretion of the oncometabolite R (-)-2-hydroxyglutarate (2HG). We developed a small molecule, AGI-6780, that potently and selectively inhibits the tumor-associated mutant IDH2/R140Q. A crystal structure of AGI-6780 complexed with IDH2/R140Q revealed that the inhibitor binds in an allosteric manner at the dimer interface. The results of steady-state enzymology analysis were consistent with allostery and slow-tight binding by AGI-6780. Treatment with AGI-6780 induced differentiation of TF-1 erythroleukemia and primary human acute myelogenous leukemia (AML) cells in vitro. These data provide proof-of-concept that inhibitors targeting mutant IDH2/R140Q could have potential applications as a differentiation therapy for cancer. | ||
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| - | Targeted Inhibition of Mutant IDH2 in Leukemia Cells Induces Cellular Differentiation.,Wang F, Travins J, Delabarre B, Penard-Lacronique V, Schalm S, Hansen E, Straley K, Kernytsky A, Liu W, Gliser C, Yang H, Gross S, Artin E, Saada V, Mylonas E, Quivoron C, Popovici-Muller J, Saunders JO, Salituro FG, Yan S, Murray S, Wei W, Gao Y, Dang L, Dorsch M, Agresta S, Schenkein DP, Biller SA, Su SM, de Botton S, Yen KE Science. 2013 Apr 4. PMID:23558173<ref>PMID:23558173</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4ja8" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
Complex of Mitochondrial Isocitrate Dehydrogenase R140Q Mutant with AGI-6780 Inhibitor
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Categories: Homo sapiens | Large Structures | Chen L | DeLaBarre B | Jiang F | Qian K | Travins J | Wei W | Wu M
