7ce3

Crystal structure of human IDH3 holoenzyme in APO form.Crystal structure of human IDH3 holoenzyme in APO form.

Structural highlights 7ce3 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 3.472Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function IDH3G_HUMAN Publication Abstract from PubMed Human NAD-dependent isocitrate dehydrogenase or HsIDH3 catalyzes the decarboxylation of isocitrate into alpha-ketoglutarate in the TCA cycle. HsIDH3 exists and functions as a heterooctamer composed of the alphabeta and alphagamma heterodimers, and is regulated allosterically and/or competitively by numerous metabolites including CIT, ADP, ATP, and NADH. In this work, we report the crystal structure of HsIDH3 containing a beta mutant in apo form. In the HsIDH3 structure, the alphabeta and alphagamma heterodimers form the alpha(2)betagamma heterotetramer via their clasp domains, and two alpha(2)betagamma heterotetramers form the (alpha(2)betagamma)(2) heterooctamer through insertion of the N-terminus of the gamma subunit of one heterotetramer into the back cleft of the beta subunit of the other heterotetramer. The functional roles of the key residues at the allosteric site, the pseudo allosteric site, the heterodimer and heterodimer-heterodimer interfaces, and the N-terminal of the gamma subunit are validated by mutagenesis and kinetic studies. Our structural and biochemical data together demonstrate that the allosteric site plays an important role but the pseudo allosteric site plays no role in the allosteric activation of the enzyme; the activation signal from the allosteric site is transmitted to the active sites of both alphabeta and alphagamma heterodimers via the clasp domains; and the N-terminal of the gamma subunit plays a critical role in the formation of the heterooctamer to ensure the optimal activity of the enzyme. These findings reveal the molecular mechanism of the assembly and allosteric regulation of HsIDH3. Structure and allosteric regulation of human NAD-dependent isocitrate dehydrogenase.,Sun P, Liu Y, Ma T, Ding J Cell Discov. 2020 Dec 22;6(1):94. doi: 10.1038/s41421-020-00220-7. PMID:33349631 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Isocitrate dehydrogenase 3D structures

spinqualitylabelsall models 7ce3, resolution 3.47Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image