title: Structure, redox, pKa, spin. A golden tetrad for understanding metalloenzyme energetics and reaction pathways.
abstract: After a review of the current status of density functional theory (DFT) for spin-polarized and spin-coupled systems, we focus on the resting states and intermediates of redox-active metalloenzymes and electron transfer proteins, showing how comparisons of DFT-calculated spectroscopic parameters with experiment and evaluation of related energies and geometries provide important information. The topics we examine include (1) models for the active-site structure of methane monooxygenase intermediate Q and ribonucleotide reductase intermediate X; (2) the coupling of electron transfer to proton transfer in manganese superoxide dismutase, with implications for reaction kinetics; (3) redox, pK(a), and electronic structure issues in the Rieske iron-sulfur protein, including their connection to coupled electron/proton transfer, and an analysis of how partial electron delocalization strongly alters the electron paramagnetic resonance spectrum; (4) the connection between protein-induced structural distortion and the electronic structure of oxidized high-potential 4Fe4S proteins with implications for cluster reactivity; (5) an analysis of cluster assembly and central-atom insertion into the FeMo cofactor center of nitrogenase based on DFT structural and redox potential calculations.
authors.affiliation: Department of Molecular Biology, TPC15, The Scripps Research Institute, La Jolla, CA 92037, USA. lou@scripps.edu
authors.forename: Louis
authors.initials: L
authors.lastname: Noodleman
authors.forename: Wen-Ge
authors.initials: WG
authors.lastname: Han
mesh_terms: D001665:Binding Sites; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D007506:Iron-Sulfur Proteins; D009942:Organometallic Compounds; D010105:Oxygenases; C021555:methane monooxygenase