title: Molecular dynamics simulations give insight into the conformational change, complex formation, and electron transfer pathway for cytochrome P450 reductase.
abstract: Cytochrome P450 reductase (CYPOR) undergoes a large conformational change to allow for an electron transfer to a redox partner to take place. After an internal electron transfer over its cofactors, it opens up to facilitate the interaction and electron transfer with a cytochrome P450. The open conformation appears difficult to crystallize. Therefore, a model of a human CYPOR in the open conformation was constructed to be able to investigate the stability and conformational change of this protein by means of molecular dynamics simulations. Since the role of the protein is to provide electrons to a redox partner, the interactions with cytochrome P450 2D6 (2D6) were investigated and a possible complex structure is suggested. Additionally, electron pathway calculations with a newly written program were performed to investigate which amino acids relay the electrons from the FMN cofactor of CYPOR to the HEME of 2D6. Several possible interacting amino acids in the complex, as well as a possible electron transfer pathway were identified and open the way for further investigation by site directed mutagenesis studies.
authors.affiliation: Department of Material Sciences and Process Engineering, Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences Vienna, Muthgasse 18, A-1190, Vienna, Austria.
authors.forename: Axel
authors.initials: A
authors.lastname: Sündermann
authors.forename: Chris
authors.initials: C
authors.lastname: Oostenbrink
mesh_terms: D000818:Animals; D004579:Electron Transport; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009251:NADPH-Ferrihemoprotein Reductase / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D051381:Rats
chemical_list: D009251:NADPH-Ferrihemoprotein Reductase
keywords: complex formation; conformation changes; cytochrome P450 reductase; molecular dynamics simulations; protein in membrane