Structure of a highly NADP+-specific isocitrate dehydrogenase

Acta Crystallographica. Section D, Biological Crystallography
Navdeep S SidhuGeorge M Sheldrick

Abstract

Isocitrate dehydrogenase catalyzes the first oxidative and decarboxylation steps in the citric acid cycle. It also lies at a crucial bifurcation point between CO2-generating steps in the cycle and carbon-conserving steps in the glyoxylate bypass. Hence, the enzyme is a focus of regulation. The bacterial enzyme is typically dependent on the coenzyme nicotinamide adenine dinucleotide phosphate. The monomeric enzyme from Corynebacterium glutamicum is highly specific towards this coenzyme and the substrate isocitrate while retaining a high overall efficiency. Here, a 1.9 Å resolution crystal structure of the enzyme in complex with its coenzyme and the cofactor Mg2+ is reported. Coenzyme specificity is mediated by interactions with the negatively charged 2'-phosphate group, which is surrounded by the side chains of two arginines, one histidine and, via a water, one lysine residue, forming ion pairs and hydrogen bonds. Comparison with a previous apoenzyme structure indicates that the binding site is essentially preconfigured for coenzyme binding. In a second enzyme molecule in the asymmetric unit negatively charged aspartate and glutamate residues from a symmetry-related enzyme molecule interact with the positively charged arginines,...Continue Reading

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Related Concepts

Idp1 protein, S pombe
Hydrogen Bonding
Isocitrate Dehydrogenase-I
Magnesium
NADP
Protein Conformation
Tertiary Protein Structure
Crystallography, X-Ray
Holoenzymes
Corynebacterium glutamicum

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