info:eu-repo/semantics/article
Conformational changes on substrate binding revealed by structures of Methylobacterium extorquens malate dehydrogenase
Fecha
2018-10Registro en:
Gonzalez, Javier Marcelo; Martí Arbona, Ricardo; Chen, Julian; Broom Peltz, Brian; Unkefer, Clifford; Conformational changes on substrate binding revealed by structures of Methylobacterium extorquens malate dehydrogenase; International Union of Crystallography; Acta Crystallographica Section F: Structural Biology Communications; 74; 10; 10-2018; 610-616
2053-230X
CONICET Digital
CONICET
Autor
Gonzalez, Javier Marcelo
Martí Arbona, Ricardo
Chen, Julian
Broom Peltz, Brian
Unkefer, Clifford
Resumen
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.Crystal structures of apo malate dehydrogenase (MDH) from Methylobacterium extorquens, MDH bound to NAD+, and MDH with oxaloacetate and ADP-ribose revealed conformational changes, closing the active site upon coenzyme and substrate binding. In the ternary complex, His284 is in position to donate a proton in the formation of (2S)-malate.