Investigation of the requirements for efficient and selective cytochrome P450 monooxygenase catalysis across different reactions.

Investigation of the requirements for efficient and selective cytochrome P450 monooxygenase catalysis across different reactions.
J Inorg Biochem. 2019 Nov 13;203:110913
Authors: Podgorski MN, Coleman T, Chao RR, De Voss JJ, Bruning JB, Bell SG
Abstract
The cytochrome P450 metalloenzyme (CYP) CYP199A4 from Rhodopseudomonas palustris HaA2 catalyzes the highly efficient oxidation of para-substituted benzoic acids. Here we determined crystal structures of CYP199A4, and the binding and turnover parameters, with different meta-substituted benzoic acids in order to establish which criteria are important for efficient catalysis. When compared to the para isomers, the meta-substituted benzoic acids were less efficiently oxidized. For example, 3-formylbenzoic acid was oxidized with lower activity than the equivalent para isomer and 3-methoxybenzoic acid did not undergo O-demethylation by CYP199A4. The structural data highlighted that the meta-substituted benzoic acids bound in the enzyme active site in a modified position with incomplete loss of the distal water ligand of the heme moiety. However, for both sets of isomers the meta- or para-substituent pointed towards, and was in close proximity, to the heme iron. The absence of oxidation activity with 3-methoxybenzoic acid was assigned to the observation that the CH bonds of this molecule point away from the heme iron. In contrast, in the para isomer they are in an ideal location for abstract...

Source: Journal of Inorganic Biochemistry - November 12, 2019 Category: Biochemistry Authors: Podgorski MN, Coleman T, Chao RR, De Voss JJ, Bruning JB, Bell SG Tags: J Inorg Biochem Source Type: research