Catalytic coupling of the active sites in Acetyl-CoA synthase, a bifunctional CO-Channeling enzyme

Acetogenic bacteria contain acetyl-CoA synthase (ACS), an enzyme with two d istinct nickel-iron-sulfur active sites connected by a tunnel through which CO migrates. One site reduces CO2 to CO, while the other synthesizes acety l-CoA from CO, CoA, and the methyl group of another protein (CH3-CP). Rapid binding Of CO2 and a two-electron reduction activates ACS. When CoA and CH 3-CP bind ACS, CO is rerouted through the tunnel to the synthase site, and kinetic parameters at the reductase site are altered. Under these condition s, the rates Of CO2 reduction and acetyl-CoA synthesis are synchronized by an ordered catalytic mechanism.