Abstract
A metallocofactor containing iron, sulfur, copper, and nickel has been discovered in the enzyme carbon monoxide dehydrogenase/acetyl-CoA (coenzyme A) synthase from Moorella thermoacetica (f. Clostridium thermoaceticum). Our structure at 2.2 angstrom resolution reveals that the cofactor responsible for the assembly of acetyl-CoA contains a [Fe4S4] cubane bridged to a copper-nickel binuclear site. The presence of these three metals together in one cluster was unanticipated and suggests a newly discovered role for copper in biology. The different active sites of this bifunctional enzyme complex are connected via a channel, 138 angstroms long, that provides a conduit for carbon monoxide generated at the C-cluster on one subunit to be incorporated into acetyl-CoA at the A-cluster on the other subunit.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetates / metabolism
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Acetyl Coenzyme A / metabolism
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Aldehyde Oxidoreductases / chemistry*
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Aldehyde Oxidoreductases / metabolism*
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Anaerobiosis
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Binding Sites
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Carbon Dioxide / metabolism
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Carbon Monoxide / metabolism
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Catalysis
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Clostridium / enzymology*
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Copper / chemistry*
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Crystallography, X-Ray
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Dimerization
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Electron Spin Resonance Spectroscopy
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Hydrophobic and Hydrophilic Interactions
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Iron / chemistry*
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Ligands
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Models, Molecular
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Multienzyme Complexes / chemistry*
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Multienzyme Complexes / metabolism*
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Nickel / chemistry*
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Oxidation-Reduction
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Protein Conformation
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Protein Folding
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Protein Structure, Quaternary
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Protein Subunits
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Zinc / chemistry
Substances
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Acetates
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Ligands
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Multienzyme Complexes
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Protein Subunits
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Carbon Dioxide
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Acetyl Coenzyme A
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Copper
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Nickel
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Carbon Monoxide
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Iron
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Aldehyde Oxidoreductases
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carbon monoxide dehydrogenase
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Zinc