5h3e

Crystal structure of mouse isocitrate dehydrogenases 2 K256Q mutant complexed with isocitrate

spinqualitylabelsall models 5h3e, resolution 2.21Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5h3e is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.21Å Ligands: ICT, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function IDHP_MOUSE Plays a role in intermediary metabolism and energy production. It may tightly associate or interact with the pyruvate dehydrogenase complex. Publication Abstract from PubMed Mitochondrial isocitrate dehydrogenase 2 (IDH2) converts NADP+ to NADPH and promotes regeneration of reduced glutathione (GSH) by supplying NADPH to glutathione reductase or thioredoxin reductase. We have previously shown that under calorie restriction, mitochondrial deacetylase Sirt3 deacetylates and activates IDH2, thereby regulating the mitochondrial glutathione antioxidant defense system in mice. To investigate the regulatory mechanism of mIDH2 (mouse mitochondrial IDH2), we used lysine-to-glutamine (KQ) mutants to mimic acetylated lysines and screened 15 KQ mutants. Among these mutants, the activities of the K256Q and K413Q proteins were less than 50% of the wild-type value. We then solved the crystal structures of the wild-type mIDH2 and the K256Q mutant proteins, revealing conformational changes in the substrate-binding pocket. Structural data suggested that positively charged Lys256 was important in stabilizing the pocket because it repelled a lysine cluster on the other side. Glutamine (or acetylated lysine) was neutral and thus caused the pocket size to decrease, which might be the main reason for the lower activity of the K256Q mutant. Together, our data provide the first structure of an acetylation mimic of mIDH2 and new insights into the regulatory mechanism of acetylation of mIDH2. Studies on the regulatory mechanism of isocitrate dehydrogenase 2 using acetylation mimics.,Xu Y, Liu L, Nakamura A, Someya S, Miyakawa T, Tanokura M Sci Rep. 2017 Aug 29;7(1):9785. doi: 10.1038/s41598-017-10337-7. PMID:28852116 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Isocitrate dehydrogenase 3D structures

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