Evolutionary history of a specialized p450 propane monooxygenase.

ABSTRACT: The evolutionary pressures that shaped the specificity and catalytic efficiency of enzymes can only be speculated. While directed evolution experiments show that new functions can be acquired under positive selection with few mutations, the role of negative selection in eliminating undesired activities and achieving high specificity remains unclear. Here we examine intermediates along the 'lineage' from a naturally occurring C12-C20 fatty acid hydroxylase (P450BM3) to a laboratory-evolved P450 propane monooxygenase (P450PMO) having 20 heme domain substitutions compared to P450BM3. Biochemical, crystallographic, and computational analyses show that a minimal perturbation of the P450BM3 fold and substrate-binding pocket accompanies a significant broadening of enzyme substrate range and the e

SUBMITTER: Fasan R 

PROVIDER: S-EPMC2637765 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature