Exploring the role of conformational heterogeneity in cis-autoproteolytic activation of ThnT.

ABSTRACT: In the past decade, there have been major achievements in understanding the relationship between enzyme catalysis and protein structural plasticity. In autoprocessing systems, however, there is a sparsity of direct evidence of the role of conformational dynamics, which are complicated by their intrinsic chemical reactivity. ThnT is an autoproteolytically activated enzyme involved in the biosynthesis of the β-lactam antibiotic thienamycin. Conservative mutation of ThnT results in multiple conformational states that can be observed via X-ray crystallography, establishing ThnT as a representative and revealing system for studing how conformational dynamics control autoactivation at a molecular level. Removal of the nucleophile by mutation to Ala disrupts the population of a reactive state and

SUBMITTER: Buller AR 

PROVIDER: S-EPMC4095933 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature