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Structural and dynamic properties of cytochrome P450 BM‐3 in pure water and in a dimethylsulfoxide/water mixture
Author(s) -
Roccatano Danilo,
Wong Tuck Seng,
Schwaneberg Ulrich,
Zacharias Martin
Publication year - 2005
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.20290
Subject(s) - chemistry , active site , flavin mononucleotide , molecular dynamics , solvent , molecule , monooxygenase , flavin group , heme , enzyme , small molecule , stereochemistry , cytochrome p450 , combinatorial chemistry , computational chemistry , organic chemistry , biochemistry
Solvent molecules play an important role for the structural and dynamical properties of proteins. A major focus of current protein engineering is the development of enzymes that are catalytically active in the presence of organic solvents. The monooxygenase P450 BM‐3 is one of the best‐studied enzymes and promising for industrial applications but with limited activity in the presence of organic solvents or cosolvents. To gain insights into the structural and dynamical properties of the heme domain of this enzyme in solution, molecular dynamics simulations in pure water and in a 14% DMSO/water mixture were performed. The results of the simulations show overall similar structural fluctuations in both solvent systems, with no indication of partial or global unfolding. In 14% DMSO, the regions comprising the helices E, F, and the EF loop (implicated in controlling the entry to the active site channel) undergo a large shift. Significant changes were also observed near the active site access channel at the residue R47. During the simulation, no DMSO molecule penetrated the active site. However, a significant accumulation of DMSO molecules close to the substrate‐binding site and to the Flavin Mononucleotide (FMN) reductase domain interface was observed. © 2005 Wiley Periodicals, Inc. Biopolymers 78: 259–267, 2005