title: Structures and energetics of models for the active site of acetyl-coenzyme a synthase: role of distal and proximal metals in catalysis.
abstract: Acetyl-coenzyme A (CoA) synthase/carbon monoxide dehydrogenase (ACS/CODH) is a bifunctional enzyme that generates CO from carbon dioxide in the C-cluster of the beta subunit and synthesizes acetyl-CoA from carbon monoxide (CO), CoA, and CH3+ at the active site of the A-cluster in the alpha subunit. On the basis of density functional calculations, we predict that methylation of Nip occurs first, and CO then adds to the NipII-CH3 species to form the intermediate, NipII(CO)(CH3), in which Nip deligates one of its SNid bonds. The CO-insertion/CH3-migration occurs on one metal, the proximal Ni, forming the trigonal planar NipII-acetyl intermediate. The thiolate can bind to NipII and reductively eliminate the thioester. Our calculations disfavor the unprecedented bimetallic CO-insertion/CH3-migration. Ni in the proximal site produces a better catalyst than does Cu.
authors.affiliation: Contribution from the Department of Chemistry, Texas A&M University, College Station, Texas 77843-3255, USA.
authors.forename: Charles Edwin
authors.initials: CE
authors.lastname: Webster
authors.forename: Marcetta Y
authors.initials: MY
authors.lastname: Darensbourg
authors.forename: Paul A
authors.initials: PA
authors.lastname: Lindahl
authors.forename: Michael B
authors.initials: MB
authors.lastname: Hall
mesh_terms: D000106:Acetate-CoA Ligase / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D002384:Catalysis; D003300:Copper / Q000737:chemistry / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism; D019216:Metals, Heavy / Q000737:chemistry* / Q000378:metabolism*; D009532:Nickel / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
chemical_list: D007506:Iron-Sulfur Proteins; D019216:Metals, Heavy; D003300:Copper; D009532:Nickel; D000106:Acetate-CoA Ligase; D015032:Zinc