4i3k

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Current revision (11:49, 1 March 2024) (edit) (undo)
 
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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>
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</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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3056&#8491;</td></tr>
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<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]
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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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 &gt;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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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</div>
 
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<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]]
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>

Current revision

Crystal structure of a metabolic reductase with 1-hydroxy-6-(4-hydroxybenzyl)-4-methylpyridin-2(1H)-one

PDB ID 4i3k

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