title: Insights into the respiratory electron transfer pathway from the structure of nitrate reductase A.
abstract: The facultative anaerobe Escherichia coli is able to assemble specific respiratory chains by synthesis of appropriate dehydrogenases and reductases in response to the availability of specific substrates. Under anaerobic conditions in the presence of nitrate, E. coli synthesizes the cytoplasmic membrane-bound quinol-nitrate oxidoreductase (nitrate reductase A; NarGHI), which reduces nitrate to nitrite and forms part of a redox loop generating a proton-motive force. We present here the crystal structure of NarGHI at a resolution of 1.9 A. The NarGHI structure identifies the number, coordination scheme and environment of the redox-active prosthetic groups, a unique coordination of the molybdenum atom, the first structural evidence for the role of an open bicyclic form of the molybdo-bis(molybdopterin guanine dinucleotide) (Mo-bisMGD) cofactor in the catalytic mechanism and a novel fold of the membrane anchor subunit. Our findings provide fundamental molecular details for understanding the mechanism of proton-motive force generation by a redox loop.
authors.affiliation: Department of Biochemistry, University of British Columbia, 2146 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Michela G
authors.initials: MG
authors.lastname: Bertero
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rothery
authors.forename: Monica
authors.initials: M
authors.lastname: Palak
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hou
authors.forename: Daniel
authors.initials: D
authors.lastname: Lim
authors.forename: Francis
authors.initials: F
authors.lastname: Blasco
authors.forename: Joel H
authors.initials: JH
authors.lastname: Weiner
authors.forename: Natalie C J
authors.initials: NC
authors.lastname: Strynadka
mesh_terms: D002384:Catalysis; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000201:enzymology; D004579:Electron Transport; D004583:Electrons; D004926:Escherichia coli / Q000201:enzymology; D008954:Models, Biological; D008958:Models, Molecular; D050901:Nitrate Reductase; D009565:Nitrate Reductases / Q000737:chemistry*; D010084:Oxidation-Reduction; D017434:Protein Structure, Tertiary; D011522:Protons
chemical_list: D011522:Protons; D009565:Nitrate Reductases; D050901:Nitrate Reductase