Role of Ligand-Driven Conformational Changes in Enzyme Catalysis: Modeling the Reactivity of the Catalytic Cage of Triosephosphate Isomerase.

ABSTRACT: We have previously performed empirical valence bond calculations of the kinetic activation barriers, Δ G^‡_calc, for the deprotonation of complexes between TIM and the whole substrate glyceraldehyde-3-phosphate (GAP, Kulkarni et al. J. Am. Chem. Soc. 2017 , 139 , 10514 - 10525 ). We now extend this work to also study the deprotonation of the substrate pieces glycolaldehyde (GA) and GA·HP_i [HP_i = phosphite dianion]. Our combined calculations provide activation barriers, Δ G^‡_calc, for the TIM-catalyzed deprotonation of GAP (12.9 ± 0.8 kcal·mol^-1), of the substrate piece GA (15.0 ± 2.4 kcal·mol^-1), and of the pieces GA·HP_i (15.5 ± 3.5 kcal·mol^-1). The effect of bound dianion on Δ G

SUBMITTER: Kulkarni YS 

PROVIDER: S-EPMC5867644 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature