Interface Residues That Drive Allosteric Transitions Also Control the Assembly of l-Lactate Dehydrogenase.

ABSTRACT: The allosteric enzyme, l-lactate dehydrogenase (LDH), is activated by fructose 1,6-metaphosphate (FBP) to reduce pyruvate to lactate. The molecular details of the FBP-driven transition from the low affinity T state to the high affinity R state in LDH, a tetramer composed of identical subunits, are not known. The dynamics of the T → R allosteric transition, investigated using Brownian dynamics (BD) simulations of the self-organized polymer (SOP) model, revealed that coordinated rotations of the subunits drive the T → R transition. We used the structural perturbation method (SPM), which requires only the static structure, to identify the allostery wiring diagram (AWD), a network of residues that transmits signals across the tetramer, as LDH undergoes the T → R transition. Interestingly, the

SUBMITTER: Chen J 

PROVIDER: S-EPMC6422748 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature