Conformational changes on substrate binding revealed by structures of Methylobacterium extorquens malate dehydrogenase

Three high-resolution X-ray crystal structures of malate dehydrogenase (MDH; EC 1.1.1.37) from the methylotroph Methylobacterium extorquens AM1 are presented. By comparing the structures of apo MDH, a binary complex of MDH and NAD+, and a ternary complex of MDH and oxaloacetate with ADP-ribose occupying the pyridine nucleotide-binding site, conformational changes associated with the formation of the catalytic complex were characterized. While the substrate-binding site is accessible in the enzyme resting state or NAD+-bound forms, the substrate-bound form exhibits a closed conformation. This conformational change involves the transition of an α -helix to a 310-helix, which causes the adjacent loop to close the active site following coenzyme and substrate binding. In the ternary complex, His284 forms a hydrogen bond to the C2 carbonyl of oxaloacetate, placing it in a position to donate a proton in the formation of (2S)-malate.

Source: Acta Crystallographica Section F - September 19, 2018 Category: Biochemistry Authors: Gonz á lez, J.M. Marti-Arbona, R. Chen, J.C.-H. Broom-Peltz, B. Unkefer, C.J. Tags: malate dehydrogenase methylotrophs biofuels Methylobacterium extorquens research communications Source Type: research