title: Computational studies of reaction mechanisms of methane monooxygenase and ribonucleotide reductase.
abstract: An overview of the computational efforts made by our group during the last few years in the field of nonheme diiron proteins is presented. Through application of ab initio methodology to a reasonable set of molecular models, significant progress is made in understanding how the soluble Methane Monooxygenase system achieves the hydroxylation of methane and how the catalytic cycle of Ribonucleotide Reductase is initiated. In particular, the current studies reveal in more detail (1) the nature of key intermediates in the reaction cycles of these two metalloenzymes, (2) details of how the iron centers regulate the systems, and (3) important aspects of how the carboxylate ligands in the active sites may tailor the enzymatic needs of the metalloprotein. This knowledge also leads to novel connections between the two enzymes. The coordinative unsaturation and carboxylate shifts investigated herein are two properties that are likely to be of more general impact in nonheme proteins. The control of the redox chemistry of the enzyme by the binuclear metal center, also analyzed here, should find common ground among other bimetallic systems as well.
authors.affiliation: Cherry L. Emerson Center for Scientific Computation and Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Maricel
authors.initials: M
authors.lastname: Torrent
authors.forename: Djamaladdin G
authors.initials: DG
authors.lastname: Musaev
authors.forename: Harold
authors.initials: H
authors.lastname: Basch
authors.forename: Keiji
authors.initials: K
authors.lastname: Morokuma
mesh_terms: D001665:Binding Sites; D001671:Biochemistry / Q000379:methods; D002384:Catalysis; D004578:Electron Spin Resonance Spectroscopy; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008667:Metalloproteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D019159:Nonheme Iron Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000737:chemistry* / Q000378:metabolism*; D012264:Ribonucleotide Reductases / Q000737:chemistry* / Q000378:metabolism*; D014867:Water / Q000378:metabolism
chemical_list: D008667:Metalloproteins; D019159:Nonheme Iron Proteins; D014867:Water; D007501:Iron; D010105:Oxygenases; C021555:methane monooxygenase; D012264:Ribonucleotide Reductases