Roles of Closed- and Open-Loop Conformations in Large-Scale Structural Transitions of l-Lactate Dehydrogenase.

ABSTRACT: The mechanism of l-lactate generation from pyruvate by l-lactate dehydrogenase (LDH) from the rabbit muscle was studied theoretically by the multistructural microiteration (MSM) method combined with the quantum mechanics/molecular mechanics (QM/MM)-ONIOM method, where the MSM method describes the MM environment as a weighted average of multiple different structures that are fully relaxed during geometry optimization or a reaction path calculation for the QM part. The results showed that the substrate binding and product states were stabilized only in the open-loop conformation of LDH and the reaction occurred in the closed-loop conformation. In other words, before and after the chemical reaction, a large-scale structural transition from the open-loop conformation to the closed-loop conform

SUBMITTER: Suzuki K 

PROVIDER: S-EPMC6648161 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature