title: Crystal structure of quinohemoprotein alcohol dehydrogenase from Comamonas testosteroni: structural basis for substrate oxidation and electron transfer.
abstract: Quinoprotein alcohol dehydrogenases are redox enzymes that participate in distinctive catabolic pathways that enable bacteria to grow on various alcohols as the sole source of carbon and energy. The x-ray structure of the quinohemoprotein alcohol dehydrogenase from Comamonas testosteroni has been determined at 1.44 A resolution. It comprises two domains. The N-terminal domain has a beta-propeller fold and binds one pyrroloquinoline quinone cofactor and one calcium ion in the active site. A tetrahydrofuran-2-carboxylic acid molecule is present in the substrate-binding cleft. The position of this oxidation product provides valuable information on the amino acid residues involved in the reaction mechanism and their function. The C-terminal domain is an alpha-helical type I cytochrome c with His(608) and Met(647) as heme-iron ligands. This is the first reported structure of an electron transfer system between a quinoprotein alcohol dehydrogenase and cytochrome c. The shortest distance between pyrroloquinoline quinone and heme c is 12.9 A, one of the longest physiological edge-to-edge distances yet determined between two redox centers. A highly unusual disulfide bond between two adjacent cysteines bridges the redox centers. It appears essential for electron transfer. A water channel delineates a possible pathway for proton transfer from the active site to the solvent.
authors.affiliation: Laboratory of Biophysical Chemistry and BIOSON Research Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
authors.forename: Arthur
authors.initials: A
authors.lastname: Oubrie
authors.forename: Henriëtte J
authors.initials: HJ
authors.lastname: Rozeboom
authors.forename: Kor H
authors.initials: KH
authors.lastname: Kalk
authors.forename: Eric G
authors.initials: EG
authors.lastname: Huizinga
authors.forename: Bauke W
authors.initials: BW
authors.lastname: Dijkstra
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D002118:Calcium / Q000032:analysis; D020585:Comamonas / Q000201:enzymology*; D018360:Crystallography, X-Ray / Q000379:methods; D004579:Electron Transport; D008958:Models, Molecular; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D000429:Alcohol Oxidoreductases; C019641:alcohol dehydrogenase (acceptor); D002118:Calcium