title: Ligand diffusion in the catalase from Proteus mirabilis: a molecular dynamics study.
abstract: The role of the channels and cavities present in the catalase from Proteus mirabilis (PMC) was investigated using molecular dynamics (MD) simulations. The reactant and products of the reaction, H(2)O(2) -->1/2 O(2) + H(2)O, catalyzed by the enzyme were allowed to diffuse to and from the active site. Dynamic fluctuations in the structure are found necessary for the opening of the major channel, identified in the X-ray model, which allows access to the active site. This channel is the only pathway to the active site observed during the dynamics, and both the products and reactant use it. H(2)O and O(2) are also detected in a cavity defined by the heme and Ser196, which could play an important role during the reaction. Free energy profiles of the ligands diffusing through the major channel indicate that the barriers to ligand diffusion are less than 20 kJ mol(-1) for each of the species. It is not clear from our study that minor channels play a role for access to the protein active site or to the protein surface.
authors.affiliation: Laboratoire de Dynamique Moléculaire, Institut de Biologie Structurale, Jean-Pierre Ebel, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France.
authors.forename: P
authors.initials: P
authors.lastname: Amara
authors.forename: P
authors.initials: P
authors.lastname: Andreoletti
authors.forename: H M
authors.initials: HM
authors.lastname: Jouve
authors.forename: M J
authors.initials: MJ
authors.lastname: Field
mesh_terms: D001665:Binding Sites; D002374:Catalase / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D004058:Diffusion; D004734:Energy Metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry; D011487:Protein Conformation; D011513:Proteus mirabilis / Q000201:enzymology*; D015203:Reproducibility of Results; D014867:Water / Q000737:chemistry
chemical_list: D008024:Ligands; D014867:Water; D006861:Hydrogen Peroxide; D002374:Catalase; D010100:Oxygen