title: Heme-copper oxidases with modified D- and K-pathways are yet efficient proton pumps.
abstract: The cytochrome aa(3)-type quinol oxidase from the archaeon Acidianus ambivalens and the ba(3)-type cytochrome c oxidase from Thermus thermophilus are divergent members of the heme-copper oxidase superfamily of enzymes. In particular they lack most of the key residues involved in the proposed proton transfer pathways. The pumping capability of the A. ambivalens enzyme was investigated and found to occur with the same efficiency as the canonical enzymes. This is the first demonstration of pumping of 1 H(+)/electron in a heme-copper oxidase that lacks most residues of the K- and D-channels. Also, the structure of the ba(3) oxidase from T. thermophilus was simulated by mutating Phe274 to threonine and Glu278 to isoleucine in the D-pathway of the Paracoccus denitrificans cytochrome c oxidase. This modification resulted in full efficiency of proton translocation albeit with a substantially lowered turnover. Together, these findings show that multiple structural solutions for efficient proton conduction arose during evolution of the respiratory oxidases, and that very few residues remain invariant among these enzymes to function in a common proton-pumping mechanism.
authors.affiliation: Instituto de Tecnologia Quimica e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: C M
authors.initials: CM
authors.lastname: Gomes
authors.forename: C
authors.initials: C
authors.lastname: Backgren
authors.forename: M
authors.initials: M
authors.lastname: Teixeira
authors.forename: A
authors.initials: A
authors.lastname: Puustinen
authors.forename: M L
authors.initials: ML
authors.lastname: Verkhovskaya
authors.forename: M
authors.initials: M
authors.lastname: Wikström
authors.forename: M I
authors.initials: MI
authors.lastname: Verkhovsky
mesh_terms: D019943:Amino Acid Substitution; D001105:Archaea; D003573:Cytochrome b Group / Q000235:genetics / Q000378:metabolism; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010231:Paracoccus denitrificans; D017494:Proton Pumps / Q000378:metabolism*; D011522:Protons; D019163:Reducing Agents / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects; D016963:Thermus thermophilus
chemical_list: D003573:Cytochrome b Group; D007473:Ion Channels; D017494:Proton Pumps; D011522:Protons; D019163:Reducing Agents; D010088:Oxidoreductases; C058557:cytochrome ba3; C020094:duroquinol oxidase; D003576:Electron Transport Complex IV