Opening of a cryptic pocket in β-lactamase increases penicillinase activity.

ABSTRACT: Understanding the functional role of protein-excited states has important implications in protein design and drug discovery. However, because these states are difficult to find and study, it is still unclear if excited states simply result from thermal fluctuations and generally detract from function or if these states can actually enhance protein function. To investigate this question, we consider excited states in β-lactamases and particularly a subset of states containing a cryptic pocket which forms under the Ω-loop. Given the known importance of the Ω-loop and the presence of this pocket in at least two homologs, we hypothesized that these excited states enhance enzyme activity. Using thiol-labeling assays to probe Ω-loop pocket dynamics and kinetic assays to probe activity, we find t

SUBMITTER: Knoverek CR 

PROVIDER: S-EPMC8617505 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature