InterPro domain: IPR010945

Malate dehydrogenases catalyse the interconversion of malate and oxaloacetate using dinucleotide cofactors [ 1 ]. The enzymes in this entry are found in archaea, bacteria and eukaryotes and fall into two distinct groups. The first group are cytoplasmic, NAD-dependent enzymes which participate in the citric acid cycle ( 1.1.1.37 ). The second group are found in plant chloroplasts, use NADP as cofactor, and participate in the C4 cycle ( 1.1.1.82 ).

Structural studies indicate that these enzymes are homodimers with very similar overall topology, though the chloroplast enzymes also have N- and C-terminal extensions, and all contain the classical Rossman fold for NAD(P)H binding [ 2 , 3 , 4 , 5 ]. Substrate specificity is determined by a mobile loop at the active site which uses charge balancing to discriminate between the correct substrates (malate and oxaloacetate) and other potential oxo/hydroxyacid substrates the enzyme may encounter within the cell [ 6 ].

1. Malate dehydrogenase: a model for structure, evolution, and catalysis. Protein Sci. 3, 1883-8
2. Determinants of protein thermostability observed in the 1.9-A crystal structure of malate dehydrogenase from the thermophilic bacterium Thermus flavus. Biochemistry 32, 3913-22
3. Structural basis for cold adaptation. Sequence, biochemical properties, and crystal structure of malate dehydrogenase from a psychrophile Aquaspirillium arcticum. J. Biol. Chem. 274, 11761-7
4. Structural basis for light activation of a chloroplast enzyme: the structure of sorghum NADP-malate dehydrogenase in its oxidized form. Biochemistry 38, 4319-26
5. Chloroplast NADP-malate dehydrogenase: structural basis of light-dependent regulation of activity by thiol oxidation and reduction. Structure 7, 461-75
6. Structural basis of substrate specificity in malate dehydrogenases: crystal structure of a ternary complex of porcine cytoplasmic malate dehydrogenase, alpha-ketomalonate and tetrahydoNAD. J. Mol. Biol. 285, 703-12