Unique structural features in a deep-sea CYP51 relate to high pressure adaptation.

ABSTRACT: Cytochromes P450 (CYP) form one of the largest enzyme superfamilies on Earth, with similar structural fold but biological functions varying from synthesis of physiologically essential compounds to metabolism of myriad xenobiotics. Here we determined the crystal structures of Coryphaenoides armatus and human sterol 14α-demethylases (CYP51s). Both structures reveal elements that imply elevated conformational flexibility, uncovering molecular basis for faster catalytic rates, lower substrate selectivity, and resistance to inhibition. These elements as well as the unique inward/outward location of the FG arm/β4 hairpin in the fish CYP51 structure were not predicted by artificial intelligence molecular modelling. The structural distinction of C. armatus CYP51, which is the first s

SUBMITTER: Hargrove TY 

PROVIDER: S-EPMC11661291 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature