Acetyl-coenzyme A synthase: the case for a Ni(p)(0)-based mechanism of catalysis.
Acetyl-CoA synthase (also known as carbon monoxide dehydrogenase) is a bifunctional Ni-Fe-S-containing enzyme that catalyzes the reversible reduction of CO(2) to CO and the synthesis of acetyl-coenzyme A from CO, CoA, and a methyl group donated by a corrinoid iron-sulfur protein. The active site for the latter reaction, called the A-cluster, consists of an Fe(4)S(4) cubane bridged to the proximal Ni site (Ni(p)), which is bridged in turn to the so-called distal Ni site. In this review, evidence is presented that Ni(p) achieves a zero-valent state at low potentials and during catalysis. Ni(p) appears to be the metal to which CO and methyl groups bind and then react to form an acetyl-Ni(p) intermediate. Methyl group binding requires reductive activation, where two electrons reduce some site on the A-cluster. The coordination environment of the distal Ni suggests that it could not be stabilized in redox states lower than 2+. The rate at which the [Fe(4)S(4)](2+) cubane is reduced is far slower than that at which reductive activation occurs, suggesting that the cubane is not the site of reduction. An intriguing possibility is that Ni(p)(2+) might be reduced to the zero-valent state. Reinforcing this idea are Ni-organometallic complexes in which the Ni exhibits analogous reactivity properties when reduced to the zero-valent state. A zero-valent Ni stabilized exclusively with biological ligands would be remarkable and unprecedented in biology.
Lindahl
Paul A
PA
Departments of Chemistry and of Biochemistry and Biophysics, Texas A and M University, College Station, TX 77843-3255, USA. lindahl@mail.chem.tamu.edu
D000106:Acetate-CoA Ligase / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002245:Carbon Dioxide / Q000737:chemistry / Q000378:metabolism; D002248:Carbon Monoxide / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008745:Methylation; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism; D009532:Nickel / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction
D007506:Iron-Sulfur Proteins; D008024:Ligands; D009097:Multienzyme Complexes; D002245:Carbon Dioxide; D009532:Nickel; D002248:Carbon Monoxide; D000106:Acetate-CoA Ligase