9icd
From Proteopedia
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CATALYTIC MECHANISM OF NADP+-DEPENDENT ISOCITRATE DEHYDROGENASE: IMPLICATIONS FROM THE STRUCTURES OF MAGNESIUM-ISOCITRATE AND NADP+ COMPLEXES
Overview
The structures of NADP+ and magnesium isocitrate bound to the, NADP(+)-dependent isocitrate dehydrogenase of Escherichia coli have been, determined and refined at 2.5-A resolution. NADP+ is bound by the large, domain of isocitrate dehydrogenase, a structure that has little similarity, to the supersecondary structure of the nucleotide-binding domain of the, lactate dehydrogenase-like family of nucleotide-binding proteins. The, coenzyme-binding site confirms the fundamentally different evolution of, the isocitrate dehydrogenase-like and the lactate dehydrogenase-like, classes of nucleotide-binding proteins. In the magnesium-isocitrate, complex, magnesium is coordinated to the alpha-carboxylate and, alpha-hydroxyl oxygen of isocitrate in a manner suitable for stabilization, of a negative charge on the hydroxyl oxygen during both the, dehydrogenation and decarboxylation steps of the conversion of isocitrate, to alpha-ketoglutarate. The metal ion is also coordinated by aspartate, side chains 283' (of the second subunit of the dimer) and 307 and two, water molecules in a roughly octahedral arrangement. On the basis of the, geometry of the active site, the base functioning in the dehydrogenation, step is most likely aspartate 283'. E. coli isocitrate dehydrogenase, transfers a hydride stereospecifically to the A-side of NADP+, and models, for a reactive ternary complex consistent with this stereospecificity are, discussed.
About this Structure
9ICD is a Single protein structure of sequence from Escherichia coli with NAP as ligand. Active as Isocitrate dehydrogenase (NADP(+)), with EC number 1.1.1.42 Full crystallographic information is available from OCA.
Reference
Catalytic mechanism of NADP(+)-dependent isocitrate dehydrogenase: implications from the structures of magnesium-isocitrate and NADP+ complexes., Hurley JH, Dean AM, Koshland DE Jr, Stroud RM, Biochemistry. 1991 Sep 3;30(35):8671-8. PMID:1888729
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