z-logo
Premium
Toward understanding the inactivation mechanism of monooxygenase P450 BM‐3 by organic cosolvents: A molecular dynamics simulation study
Author(s) -
Roccatano Danilo,
Wong Tuck Seng,
Schwaneberg Ulrich,
Zacharias Martin
Publication year - 2006
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20577
Subject(s) - chemistry , molecular dynamics , heme , mutant , monooxygenase , molecule , cytochrome p450 , catalysis , stereochemistry , active site , biocatalysis , protein engineering , combinatorial chemistry , computational chemistry , enzyme , organic chemistry , biochemistry , reaction mechanism , gene
Cytochrome P450 BM‐3 from Bacillus megaterium is an extensively studied enzyme for industrial applications. A major focus of current protein engineering research is directed to improving the catalytic performance of P450 BM‐3 toward nonnatural substrates of industrial importance in the presence of organic solvents or cosolvents. For the latter reason, it is important to study the effect of organic cosolvent molecules on the structure and dynamics of the enzyme, in particular, the effect of cosolvent molecules on the active site's structure and dynamics. In this paper, we have studied, using molecular dynamics (MD) simulations, the F87A mutant of P450 BM‐3 in the presence of DMSO as cosolvent, to understand the role of the F87A substitution for its catalytic activity. This mutant exhibits an altered regioselectivity and substrate specificity compared with wild‐type; however, it has lower tolerance toward DMSO. The simulation results offer an explanation for the DMSO sensitivity of the F87A mutant. Our simulation results show that the F87 side chain prevents the disturbance of the water molecule bound to the heme iron by DMSO molecules. The absence of the phenyl ring in F87A mutant promotes interactions of the DMSO molecule with the heme iron resulting in water displacement by DMSO at the catalytic heme center. © 2006 Wiley Periodicals, Inc. Biopolymers 83: 467–476, 2006 This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here