A Ni-Fe-Cu center in a bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase.
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.
Doukov
Tzanko I
TI
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Iverson
Tina M
TM
Seravalli
Javier
J
Ragsdale
Stephen W
SW
Drennan
Catherine L
CL
D000085:Acetates / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000737:chemistry* / Q000378:metabolism*; D000693:Anaerobiosis; D001665:Binding Sites; D002245:Carbon Dioxide / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism; D002384:Catalysis; D003013:Clostridium / Q000201:enzymology*; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D019281:Dimerization; D004578:Electron Spin Resonance Spectroscopy; D057927:Hydrophobic and Hydrophilic Interactions; D007501:Iron / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism*; D009532:Nickel / Q000737:chemistry*; D010084:Oxidation-Reduction; D011487:Protein Conformation; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D015032:Zinc / Q000737:chemistry
D000085:Acetates; D008024:Ligands; D009097:Multienzyme Complexes; D021122:Protein Subunits; D002245:Carbon Dioxide; D000105:Acetyl Coenzyme A; D003300:Copper; D009532:Nickel; D002248:Carbon Monoxide; D007501:Iron; D000445:Aldehyde Oxidoreductases; C019823:carbon monoxide dehydrogenase; D015032:Zinc