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==IDH1 R132H mutant in complex with IDH889== | |||
<StructureSection load='5tqh' size='340' side='right' caption='[[5tqh]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5tqh]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TQH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TQH FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7J2:(4S)-3-[2-({(1S)-1-[5-(4-FLUORO-3-METHYLPHENYL)PYRIMIDIN-2-YL]ETHYL}AMINO)PYRIMIDIN-4-YL]-4-(PROPAN-2-YL)-1,3-OXAZOLIDIN-2-ONE'>7J2</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr> | |||
[[Category: | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Isocitrate_dehydrogenase_(NADP(+)) Isocitrate dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.42 1.1.1.42] </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=5tqh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tqh OCA], [http://pdbe.org/5tqh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tqh RCSB], [http://www.ebi.ac.uk/pdbsum/5tqh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tqh ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/IDHC_HUMAN IDHC_HUMAN]] Defects in IDH1 are involved in the development of glioma (GLM) [MIM:[http://omim.org/entry/137800 137800]]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Note=Mutations affecting Arg-132 are tissue-specific, and suggest that this residue plays a unique role in the development of high-grade gliomas. Mutations of Arg-132 to Cys, His, Leu or Ser abolish magnesium binding and abolish the conversion of isocitrate to alpha-ketoglutarate. Instead, alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate. Elevated levels of R(-)-2-hydroxyglutarate are correlated with an elevated risk of malignant brain tumors. | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Kulathila, R]] | |||
[[Category: Xie, X]] | [[Category: Xie, X]] | ||
[[Category: | [[Category: Inhibitor]] | ||
[[Category: Isocitrate dehydrogenase]] | |||
[[Category: Nadph]] | |||
[[Category: Oxidoreductase]] | |||
[[Category: Rossmann fold]] |
Revision as of 02:47, 26 January 2017
IDH1 R132H mutant in complex with IDH889IDH1 R132H mutant in complex with IDH889
Structural highlights
Disease[IDHC_HUMAN] Defects in IDH1 are involved in the development of glioma (GLM) [MIM:137800]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Note=Mutations affecting Arg-132 are tissue-specific, and suggest that this residue plays a unique role in the development of high-grade gliomas. Mutations of Arg-132 to Cys, His, Leu or Ser abolish magnesium binding and abolish the conversion of isocitrate to alpha-ketoglutarate. Instead, alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate. Elevated levels of R(-)-2-hydroxyglutarate are correlated with an elevated risk of malignant brain tumors. |
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