Cooperative Substrate Binding Controls Catalysis in Bacterial Cytochrome P450terp (CYP108A1).

ABSTRACT: Despite being one of the most well-studied aspects of cytochrome P450 chemistry, important questions remain regarding the nature and ubiquity of allosteric regulation of catalysis. The crystal structure of a bacterial P450, P450terp, in the presence of substrate reveals two binding sites, one above the heme in position for regioselective hydroxylation and another in the substrate access channel. Unlike many bacterial P450s, P450terp does not exhibit an open to closed conformational change when substrate binds; instead, P450terp uses the second substrate molecule to hold the first substrate molecule in position for catalysis. Spectral titrations clearly show that substrate binding to P450terp is cooperative with a Hill coefficient of 1.4 and is supported by isothermal titration calorimetry.

SUBMITTER: Gable JA 

PROVIDER: S-EPMC10576961 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature