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Conformational changes on substrate binding revealed by structures of Methylobacterium extorquens malate dehydrogenase
Author(s) -
González Javier M.,
Marti-Arbona Ricardo,
Chen Julian C.-H.,
Broom-Peltz Brian,
Unkefer Clifford J.
Publication year - 2018
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x18011809
Subject(s) - ternary complex , malate dehydrogenase , stereochemistry , nad+ kinase , active site , oxidoreductase , chemistry , binding site , crystallography , substrate (aquarium) , conformational change , biochemistry , enzyme , biology , ecology
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 3 10 ‐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 (2 S )‐malate.