title: Analysis of active site motions from a 175 picosecond molecular dynamics simulation of camphor-bound cytochrome P450cam.
abstract: The structure and internal motions of the active site residues of camphor-bound cytochrome P450cam have been evaluated on the basis of a 175 psec molecular dynamics simulation. The active site residues generally show very small deviations away from their starting crystal positions. These residues also generally show much smaller fluctuations than for the enzyme as a whole. Phe 87 is dynamically very unusual and is suggested to play a role in substrate movement into and/or out of the active site. The average distance between the heme iron and atoms C5, C6, and C3 of camphor is 5.3, 6.0, and 7.0 A, respectively. This trend is consistent with the experimentally observed stereospecificity of the hydroxylation reaction. On the basis of distance and angle criteria, both 5-exo and 5-endo hydrogen abstraction are predicted to occur during the hydroxylation reaction; although the 5-exo pathway is expected to be 3-fold more likely.
authors.affiliation: Molecular Science Research Center, Pacific Northwest Laboratory, Richland, Washington 99352.
authors.forename: M D
authors.initials: MD
authors.lastname: Paulsen
authors.forename: M B
authors.initials: MB
authors.lastname: Bass
authors.forename: R L
authors.initials: RL
authors.lastname: Ornstein
mesh_terms: D001665:Binding Sites; D002164:Camphor / Q000737:chemistry* / Q000378:metabolism; D019475:Camphor 5-Monooxygenase; D003198:Computer Simulation; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D002164:Camphor; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019475:Camphor 5-Monooxygenase