4i3k
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4i3k]] 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=4I3K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I3K FirstGlance]. <br> | <table><tr><td colspan='2'>[[4i3k]] 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=4I3K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I3K FirstGlance]. <br> | ||
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1BX:1-HYDROXY-6-(4-HYDROXYBENZYL)-4-METHYLPYRIDIN-2(1H)-ONE'>1BX</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 3.3056Å</td></tr> |
+ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1BX:1-HYDROXY-6-(4-HYDROXYBENZYL)-4-METHYLPYRIDIN-2(1H)-ONE'>1BX</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4i3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i3k OCA], [https://pdbe.org/4i3k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i3k RCSB], [https://www.ebi.ac.uk/pdbsum/4i3k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i3k 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=4i3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i3k OCA], [https://pdbe.org/4i3k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i3k RCSB], [https://www.ebi.ac.uk/pdbsum/4i3k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i3k ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/IDHC_HUMAN IDHC_HUMAN] | [https://www.uniprot.org/uniprot/IDHC_HUMAN IDHC_HUMAN] | ||
- | <div style="background-color:#fffaf0;"> | ||
- | == Publication Abstract from PubMed == | ||
- | Mutations in isocitrate dehydrogenase (IDH), a key enzyme in the tricarboxylic acid cycle, have recently been found in ~75% glioma and ~20% acute myeloid leukemia. Different from the wild-type enzyme, mutant IDH1 catalyzes the reduction of alpha-ketoglutaric acid to D-2-hydroxyglutaric acid. Strong evidence has shown mutant IDH1 represents a novel target for this type of cancer. We found two 1-hydroxypyridin-2-one compounds that are potent inhibitors of R132H and R132C IDH1 mutants with Ki values as low as 120 nM. These compounds exhibit >60-fold selectivity against wild-type IDH1 and can inhibit the production of D-2-hydroxyglutaric acid in IDH1 mutated cells, representing novel chemical probes for cancer biology studies. We also report the first inhibitor-bound crystal structures of IDH1(R132H), showing these inhibitors have H-bond, electrostatic and hydrophobic interactions with the mutant enzyme. Comparison with the substrate-bound IDH1 structures revealed the structural basis for the high enzyme selectivity of these compounds. | ||
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- | Crystallographic Investigation and Selective Inhibition of Mutant Isocitrate Dehydrogenase.,Zheng B, Yao Y, Liu Z, Deng L, Anglin JL, Jiang H, Prasad BV, Song Y ACS Med Chem Lett. 2013 Jun 13;4(6):542-546. PMID:23795241<ref>PMID:23795241</ref> | ||
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- | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
- | </div> | ||
- | <div class="pdbe-citations 4i3k" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Isocitrate dehydrogenase 3D structures|Isocitrate dehydrogenase 3D structures]] | *[[Isocitrate dehydrogenase 3D structures|Isocitrate dehydrogenase 3D structures]] | ||
- | == References == | ||
- | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> |
Current revision
Crystal structure of a metabolic reductase with 1-hydroxy-6-(4-hydroxybenzyl)-4-methylpyridin-2(1H)-one
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Categories: Homo sapiens | Large Structures | Anglin JL | Deng L | Jiang H | Liu Z | Prasad BVV | Song Y | Yao Y | Zheng B