title: Proton transport in Clostridium pasteurianum [FeFe] hydrogenase I: a computational study.
abstract: To better understand the proton transport through the H2 production catalysts, the [FeFe] hydrogenases, we have undertaken a modeling and simulation study of the proton transfer processes mediated by amino acid side-chain residues in hydrogenase I from Clostridium pasteurianum. Free-energy calculation studies show that the side chains of two conserved glutamate residues, Glu-279 and Glu-282, each possess two stable conformations with energies that are sensitive to protonation state. Coordinated conformational changes of these residues can form a proton shuttle between the surface Glu-282 and Cys-299, which is the penultimate proton donor to the catalytic H-cluster. Calculated acid dissociation constants are consistent with a proton relay connecting the H-cluster to the bulk solution. The complete proton-transport process from the surface-disposed Glu-282 to Cys-299 is studied using coupled semiempirical quantum-mechanical/classical-mechanical dynamics. Two-dimensional free-energy maps show the mechanisms of proton transport, which involve Glu-279, Ser-319, and a short internal water relay to connect functionally Glu-282 with the H-cluster. The findings of conformational bistability, PT event coupling with pKa mismatch, and water participation have implications in the design of artificial water reduction or general electrocatalytic H2-production catalysts.
authors.affiliation: National Renewable Energy Laboratory , MS ESIF301, 15013 Denver West Parkway, Golden, Colorado 80401, United States.
authors.forename: Hai
authors.initials: H
authors.lastname: Long
authors.forename: Paul W
authors.initials: PW
authors.lastname: King
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Chang
mesh_terms: D003013:Clostridium / Q000201:enzymology*; D018360:Crystallography, X-Ray; D006859:Hydrogen / Q000737:chemistry / Q000378:metabolism; D006864:Hydrogenase / Q000737:chemistry / Q000378:metabolism*; D017136:Ion Transport; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011522:Protons
chemical_list: D007506:Iron-Sulfur Proteins; D011522:Protons; D006859:Hydrogen; C118830:iron hydrogenase; D006864:Hydrogenase