9ICD
CATALYTIC MECHANISM OF NADP+-DEPENDENT ISOCITRATE DEHYDROGENASE: IMPLICATIONS FROM THE STRUCTURES OF MAGNESIUM-ISOCITRATE AND NADP+ COMPLEXES
Summary for 9ICD
| Entry DOI | 10.2210/pdb9icd/pdb |
| Descriptor | ISOCITRATE DEHYDROGENASE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total) |
| Functional Keywords | oxidoreductase (nad(a)-choh(d)) |
| Biological source | Escherichia coli |
| Total number of polymer chains | 1 |
| Total formula weight | 46552.97 |
| Authors | Hurley, J.H.,Dean, A.M.,Koshland Jr., D.E.,Stroud, R.M. (deposition date: 1991-07-29, release date: 1991-10-15, Last modification date: 2024-02-14) |
| Primary citation | Hurley, J.H.,Dean, A.M.,Koshland Jr., D.E.,Stroud, R.M. Catalytic mechanism of NADP(+)-dependent isocitrate dehydrogenase: implications from the structures of magnesium-isocitrate and NADP+ complexes. Biochemistry, 30:8671-8678, 1991 Cited by PubMed Abstract: 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. PubMed: 1888729DOI: 10.1021/bi00099a026 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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