Exploring the pH-Dependent Structure-Dynamics-Function Relationship of Human Renin.

ABSTRACT: Renin is a pepsin-like aspartyl protease and an important drug target for the treatment of hypertension; despite three decades' research, its pH-dependent structure-function relationship remains poorly understood. Here, we employed continuous constant pH molecular dynamics (CpHMD) simulations to decipher the acid/base roles of renin's catalytic dyad and the conformational dynamics of the flap, which is a common structural feature among aspartyl proteases. The calculated pK_a's suggest that catalytic Asp38 and Asp226 serve as the general base and acid, respectively, in agreement with experiment and supporting the hypothesis that renin's neutral optimum pH is due to the substrate-induced pK_a shifts of the aspartic dyad. The CpHMD data confirmed our previous

SUBMITTER: Ma S 

PROVIDER: S-EPMC7855609 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature