Insight into Structural Characteristics of Protein-Substrate Interaction in Pimaricin Thioesterase.

ABSTRACT: As a polyene antibiotic of great pharmaceutical significance, pimaricin has been extensively studied to enhance its productivity and effectiveness. In our previous studies, pre-reaction state (PRS) has been validated as one of the significant conformational categories before macrocyclization, and is critical to mutual recognition and catalytic preparation in thioesterase (TE)-catalyzed systems. In our study, molecular dynamics (MD) simulations were conducted on pimaricin TE-polyketide complex and PRS, as well as pre-organization state (POS), a molecular conformation possessing a pivotal intra-molecular hydrogen bond, were detected. Conformational transition between POS and PRS was observed in one of the simulations, and POS was calculated to be energetically more stable than PRS by 4.58 kc

SUBMITTER: Fan S 

PROVIDER: S-EPMC6412417 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature