The Daily Bulletin Archive

Professor David A. Grahame from the Department of Biochemistry and Molecular Biology at Uniformed Services University of the Health Sciences will present his seminar "Protein Conformational Changes Coupled to Catalysis at the [4Fe-4S]-Ni-Ni Center of Acetyl-CoA Synthase" on Thursday, November 17, during Bengal Pause (12:15–1:30 p.m.) in Science Building 272. The following is his seminar abstract:

Acetyl-CoA synthase (ACS) is used by various species of anaerobic bacteria, including acetogens, and in methanogens and other archaea to catalyze the de novo synthesis as well as overall cleavage of the acetyl group of acetyl-CoA from simple one-carbon precursors at the level of CH3 and CO. The enzyme contains a unique active site metal cluster, designated the A cluster, that consists of a binuclear Ni-Ni center bridged to an [Fe4S4] cluster. The enzyme is unique in biochemistry in its use of organo-nickel chemistry to catalyze a carbonylation/decarbonylation reaction. In bacteria, ACS is tightly associated with CO dehydrogenase to form the bifunctional heterotetrameric enzyme CODH/ACS, whereas, in archaea ACS is a component of the large multienzyme complex acetyl-CoA decarbonylase/synthase (ACDS), which comprises five different subunits that make up the subcomponent proteins ACS, CODH, and a corrinoid enzyme. ACS enzymes exhibit multiple redox-dependent activities, including overall acetyl-CoA synthesis, acetyltransferase, and an isotopic exchange reaction between the carbonyl group of acetyl-CoA and CO. Results from systematic measurements of these activities applied to different ACS protein forms are presented, providing new insight into the mechanism of ACS catalysis, the importance of protein conformational changes in the cleavage of the acetyl C-C bond, and the overall function of the enzyme in both bacterial and archaeal systems.