Reconciling conformational heterogeneity and substrate recognition in cytochrome P450.

ABSTRACT: Cytochrome P450, the ubiquitous metalloenzyme involved in detoxification of foreign components, has remained one of the most popular systems for substrate-recognition process. However, despite being known for its high substrate specificity, the mechanistic basis of substrate-binding by archetypal system cytochrome P450cam has remained at odds with the contrasting reports of multiple diverse crystallographic structures of its substrate-free form. Here, we address this issue by elucidating the probability of mutual dynamical transition to the other crystallographic pose of cytochrome P450cam and vice versa via unbiased all-atom computer simulation. A robust Markov state model, constructed using adaptively sampled 84-μs-long molecular dynamics simulation trajectories, maps the broad and heter

SUBMITTER: Dandekar BR 

PROVIDER: S-EPMC8204291 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature