Structural insights into the mechanism of the drastic changes in enzymatic activity of the cytochrome P450 vitamin D₃ hydroxylase (CYP107BR1) caused by a mutation distant from the active site.

ABSTRACT: Cytochromes P450 (P450s) are haem-containing enzymes that catalyze medically and industrially important oxidative reactions, and many P450s have been subjected to directed evolution and site-directed mutagenesis to improve their activity and substrate specificity. Nonetheless, in most cases the mechanism that leads to drastic changes in specific activity after the introduction of an amino-acid substitution distant from the active-site pocket is unclear. Here, two crystal structures of inactive mutants of the P450 vitamin D₃ hydroxylase (Vdh), Vdh-F106V and Vdh-L348M, which were obtained in the course of protein-engineering experiments on Vdh, are reported. The overall structures of these mutants show an open conformation similar to that of wild-type Vdh (Vdh-WT), whereas a rearr

SUBMITTER: Yasutake Y 

PROVIDER: S-EPMC5417316 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature