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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aging / metabolism
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Binding Sites
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Caenorhabditis elegans / enzymology*
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Caenorhabditis elegans Proteins / chemistry
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Caenorhabditis elegans Proteins / classification
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism
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Carboxylic Acids / metabolism*
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Computational Biology
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Helminth Proteins / chemistry
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Helminth Proteins / classification*
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Helminth Proteins / genetics
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Helminth Proteins / metabolism*
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Humans
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Iron / metabolism*
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Longevity / physiology
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Models, Molecular
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Molecular Sequence Data
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Oxidoreductases / metabolism*
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Phylogeny
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Protein Conformation
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Proteins / chemistry
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Proteins / classification
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Proteins / genetics
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Proteins / metabolism
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Rats
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Sequence Homology, Amino Acid
Substances
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CLK-1 protein, C elegans
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Caenorhabditis elegans Proteins
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Carboxylic Acids
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Helminth Proteins
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Proteins
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Iron
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Oxidoreductases
Associated data
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GENBANK/AJ235270
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GENBANK/AJ252203
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GENBANK/E83564
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GENBANK/P97478
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GENBANK/Q63619
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GENBANK/T40268
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PIR/U13642
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RefSeq/NP_014768
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RefSeq/NP_057222