Three clusters of conformational states in p450cam reveal a multistep pathway for closing of the substrate access channel.

ABSTRACT: Conformational changes in the substrate access channel have been observed for several forms of cytochrome P450, but the extent of conformational plasticity exhibited by a given isozyme has not been completely characterized. Here we present crystal structures of P450cam bound to a library of 12 active site probes containing a substrate analogue tethered to a variable linker. The structures provide a unique view of the range of protein conformations accessible during substrate binding. Principal component analysis of a total of 30 structures reveals three discrete clusters of conformations: closed (P450cam-C), intermediate (P450cam-I), and fully open (P450cam-O). Relative to P450cam-C, the P450cam-I state results predominantly from a retraction of helix F, while both helices F and G move in

SUBMITTER: Lee YT 

PROVIDER: S-EPMC3032038 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature