Volume 148, 2011

Water as biocatalyst in cytochrome P450

Abstract

According to previous quantum mechanics/molecular mechanics (QM/MM) studies, camphor hydroxylation in cytochrome P450 is catalysed by a single water molecule which lowers the computed B3LYP/CHARMM barrier by about 4 kcal mol−1. Gas-phase B3LYP model studies for a variety of different substrates show the generality of this effect. Its origin is an electrostatic enhancement of hydrogen bonding in the transition state for hydrogen abstraction. Attempts are made to correlate the slight variations in the calculated barrier lowerings with substrate properties. Individual water molecules also have a decisive influence on other reactions in cytochrome P450cam, for instance, on the relative propensity for coupling and uncoupling upon protonation of Compound 0 in the wild-type enzyme and its mutants. These and other examples are reviewed briefly. Finally, we address some methodological issues on how to handle the possible involvement of water molecules in biocatalysis at the QM/MM level.

Supplementary files

Article information

Article type
Paper
Submitted
07 Apr 2010
Accepted
21 Apr 2010
First published
11 Aug 2010

Faraday Discuss., 2011,148, 373-383

Water as biocatalyst in cytochrome P450

D. Kumar, A. Altun, S. Shaik and W. Thiel, Faraday Discuss., 2011, 148, 373 DOI: 10.1039/C004950F

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