Structures and energetics of models for the active site of acetyl-coenzyme a synthase: Role of distal and proximal metals in catalysis

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 β subunit and synthesizes acetyl-CoA from carbon monoxide (CO), CoA, and CH3+ at the active site of the A-cluster in the α 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. Copyright © 2004 American Chemical Society.