6kde | pdb_00006kde

Crystal structure of the alpha beta heterodimer of human IDH3 in complex with Ca(2+)

spinqualitylabelsall models 6kde, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6kde is a 4 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 2.999Å Ligands: CA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function IDH3A_HUMAN Publication Abstract from PubMed Mammalian mitochondrial NAD-dependent isocitrate dehydrogenase (NAD-IDH) catalyzes the decarboxylation of isocitrate into alpha-ketoglutarate in the tricarboxylic acid cycle. It exists as the alpha2betagamma heterotetramer composed of the alphabeta and alphagamma heterodimers. Different from the alphagamma heterodimer that can be allosterically activated by CIT and ADP, the alphabeta heterodimer cannot be allosterically regulated by the activators; however, the molecular mechanism is unclear. We report here the crystal structures of the alphabeta heterodimer of human NAD-IDH with the alpha subunit in apo form and in Ca(2+)-bound, NAD-bound, and NADH-bound forms. Structural analyses and comparisons reveal that the alphabeta heterodimer has a similar yet more compact overall structure compared with the alphagamma heterodimer and contains a pseudo-allosteric site that is structurally different from the allosteric site. In particular, the beta3-alpha3 and beta12-alpha8 loops of the beta subunit at the pseudo-allosteric site adopt significantly different conformations from those of the gamma subunit at the allosteric site and hence impede the binding of the activators, explaining why the alphabeta heterodimer cannot be allosterically regulated by the activators. The structural data also show that NADH can compete with NAD to bind to the active site and inhibits the activity of the alphabeta heterodimer. These findings together with the biochemical data reveal the molecular basis for the function of the alphabeta heterodimer of human NAD-IDH. Molecular basis for the function of the alphabeta heterodimer of human NAD-dependent isocitrate dehydrogenase.,Sun P, Ma T, Zhang T, Zhu H, Zhang J, Liu Y, Ding J J Biol Chem. 2019 Nov 1;294(44):16214-16227. doi: 10.1074/jbc.RA119.010099. Epub , 2019 Sep 12. PMID:31515270 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Isocitrate dehydrogenase 3D structures

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