Structural and dynamic properties of cytochrome P450 BM-3 in pure water and in a dimethylsulfoxide/water mixture

Danilo Roccatano, Tuck Seng Wong, Ulrich Schwaneberg, Martin Zacharias

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)259-267
Number of pages9
JournalBiopolymers
Volume78
Issue number5
DOIs
StatePublished - 5 Aug 2005
Externally publishedYes

Keywords

  • CYP102
  • Computational solvent mapping
  • Essential dynamics
  • Nonaqueous cosolvent
  • Preferential salvation

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