Conformational changes on substrate binding revealed by structures of Methylobacterium extorquens malate dehydrogenase
- Universidad Nacional de Santiago del Estero (Argentina); Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
In this paper, three high-resolution X-ray crystal structures of malate dehydrogenase (MDH; EC 1.1.1.37) from the methylotrophMethylobacterium extorquensAM1 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. Finally, 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.
- Research Organization:
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Sponsoring Organization:
- USDOE Laboratory Directed Research and Development (LDRD) Program
- Grant/Contract Number:
- AC52-06NA25396
- OSTI ID:
- 1477666
- Report Number(s):
- LA-UR-18-24857; ACSFEN
- Journal Information:
- Acta Crystallographica. Section F, Structural Biology Communications, Vol. 74, Issue 10; ISSN 2053-230X
- Publisher:
- International Union of CrystallographyCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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