View source for 9yha


==Cryo-EM structure of IDH1 R132H==
<StructureSection load='9yha' size='340' side='right'caption='[[9yha]], [[Resolution|resolution]] 2.69&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9yha]] 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=9YHA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9YHA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.69&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=9yha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9yha OCA], [https://pdbe.org/9yha PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9yha RCSB], [https://www.ebi.ac.uk/pdbsum/9yha PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9yha ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Gain-of-function mutations of isocitrate dehydrogenase 1 (IDH1) lead to oncometabolite (R)-2-hydroxyglutarate production, contributing to the tumorigenesis of multiple human cancers. While fatty acid biosynthesis is critical for IDH1-mutant tumor growth, the underlying mechanisms remain unclear. Here, leveraging chemical probes and chemoproteomic profiling, we identified that oncogenic IDH1-R132H is uniquely autopalmitoylated at C269, which is not observed in wild-type IDH1. This modification responds to fatty acids and regulates R132H enzymatic activity by enhancing substrate and cofactor binding, as well as dimerization. Loss of C269 palmitoylation reverses IDH1-R132H-induced metabolic reprogramming and hypermethylation phenotypes and impairs cell transformation. Interestingly, C269 autopalmitoylation occurs within a hydrophobic pocket, targeted by a clinical IDH1-mutant inhibitor (LY3410738). Our study reveals that autopalmitoylation, conferred by the IDH1(R132H) mutation, links fatty acid metabolism to the regulation of IDH1 mutant activity and represents a druggable vulnerability in IDH1-mutant cancers.

Autopalmitoylation of IDH1-R132H regulates its neomorphic activity in cancer cells.,Hu L, Lin J, Sun L, Berezuk AM, Tuttle KS, Zhu X, Seo HS, Dhe-Paganon S, Li P, Sun Y, Ni L, Zhang J, Tan D, Wakimoto H, Cahill DP, Bai X, Luo X, Asara JM, Subramaniam S, Shan Y, Wu X Nat Chem Biol. 2026 Jan 13. doi: 10.1038/s41589-025-02131-8. PMID:41530531<ref>PMID:41530531</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9yha" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Berezuk AM]]
[[Category: Dhe-Paganon S]]
[[Category: Hu L]]
[[Category: Seo H-S]]
[[Category: Subramaniam S]]
[[Category: Tuttle KS]]
[[Category: Wu X]]
[[Category: Zhu X]]