How the Destabilization of a Reaction Intermediate Affects Enzymatic Efficiency: The Case of Human Transketolase.

ABSTRACT: Atomic resolution X-ray crystallography has shown that an intermediate (the X5P-ThDP adduct) of the catalytic cycle of transketolase (TK) displays a significant, putatively highly energetic, out-of-plane distortion in a sp ² carbon adjacent to a lytic bond, suggested to lower the barrier of the subsequent step, and thus was postulated to embody a clear-cut demonstration of the intermediate destabilization effect. The lytic bond of the subsequent rate-limiting step was very elongated in the X-ray structure (1.61 Å), which was proposed to be a consequence of the out-of-plane distortion. Here we use high-level QM and QM/MM calculations to study the intermediate destabilization effect. We show that the intrinsic energy penalty for the observed distortion

SUBMITTER: Prejano M 

PROVIDER: S-EPMC8016368 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature