title: CLK-1/Coq7p is a DMQ mono-oxygenase and a new member of the di-iron carboxylate protein family.
abstract: Strains of Caenorhabditis elegans mutant for clk-1 exhibit a 20-40% increase in mean lifespan. clk-1 encodes a mitochondrial protein thought to be either an enzyme or regulatory molecule acting within the ubiquinone biosynthesis pathway. Here CLK-1 is shown to be related to the ubiquinol oxidase, alternative oxidase, and belong to the functionally diverse di-iron-carboxylate protein family which includes bacterioferritin and methane mono-oxygenase. Construction and analysis of a homology model indicates CLK-1 is a 2-polyprenyl-3-methyl-6-methoxy-1,4-benzoquinone mono-oxygenase as originally predicted. Analysis of known CLK-1/Coq7p mutations also supports this notion. These findings raise the possibility of developing CLK-1-specific inhibitors to test for lifespan extension in higher organisms.
authors.affiliation: SapIENCE, Montreal, QC, Canada H2X 1X8. srea@colorado.edu
authors.forename: S
authors.initials: S
authors.lastname: Rea
mesh_terms: D000375:Aging / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D002264:Carboxylic Acids / Q000378:metabolism*; D019295:Computational Biology; D015801:Helminth Proteins / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008136:Longevity / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000378:metabolism*; D010802:Phylogeny; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid
chemical_list: C104339:CLK-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002264:Carboxylic Acids; D015801:Helminth Proteins; D011506:Proteins; D007501:Iron; D010088:Oxidoreductases