5yvt

Crystal structure of the alpha gamma heterodimer of human IDH3 in complex with Mg(2+) and NADH

spinqualitylabelsall models 5yvt, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5yvt is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: MG, NAI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function IDH3A_HUMAN Publication Abstract from PubMed Human NAD-dependent isocitrate dehydrogenase (NAD-IDH) catalyzes the oxidative decarboxylation of isocitrate in the citric acid cycle. In the alpha2betagamma heterotetramer of NAD-IDH, the gamma subunit plays the regulatory role and the beta subunit the structural role. Previous biochemical data have shown that mammalian NAD-IDHs can be inhibited by NADH; however, the molecular mechanism is unclear. In this work, we show that the alphabeta, alphagamma and alpha2betagamma enzymes of human NAD-IDH can be inhibited by NADH, and further determine the crystal structure of the alphagamma heterodimer bound with an Mg(2+) and an NADH at the active site and an NADH at the allosteric site, which resembles that of the inactive alpha(Mg)gamma heterodimer. The NADH at the active site occupies the binding site for NAD(+) and prevents the binding of the cofactor. The NADH at the allosteric site occupies the binding sites for ADP and citrate and blocks the binding of the activators. The biochemical data confirm that the NADH binding competes with the binding of NAD(+) and the binding of citrate and ADP, and the two effects together contribute to the NADH inhibition on the activity. These findings provide insights into the inhibitory mechanisms of the alphagamma heterodimer by NADH. Insights into the inhibitory mechanisms of NADH on the alphagamma heterodimer of human NAD-dependent isocitrate dehydrogenase.,Liu Y, Hu L, Ma T, Yang J, Ding J Sci Rep. 2018 Feb 16;8(1):3146. doi: 10.1038/s41598-018-21584-7. PMID:29453450 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Isocitrate dehydrogenase 3D structures

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