Acetate C-C bond formation and decomposition in the anaerobic world: the structure of a central enzyme and its key active-site metal cluster.
The structure of carbon monoxide dehydrogenase/acetyl-coenzyme A synthase (CODH/ACS), a central enzyme in the anaerobic metabolism of acetyl-coenzyme A (acetyl-CoA), has been solved to a resolution of 2.2A. The active-site metal cluster responsible for catalyzing acetyl C-C bond synthesis and cleavage, designated the A center, was identified as an Fe(4)S(4) iron sulfur cluster with one of its cysteine thiolates acting as a bridge to an adjacent binuclear metal site. Nickel was found at one position in the binuclear site and the other metal was indicated to be copper - a surprising result, implying a previously unrecognized role for copper. Details of the A center provided new insight into the unusual organometallic mechanism of acetyl C-C bond formation and cleavage, with substantial conformational changes indicated for binding of the large methylcorrinoid protein substrate, and a unique intramolecular channel acting to contain carbon monoxide within the protein and transfer it to the site needed for acetyl-CoA synthesis.
Grahame
David A
DA
Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA. dgrahame@usuhs.mil
D000085:Acetates / Q000737:chemistry* / Q000378:metabolism*; D000445:Aldehyde Oxidoreductases / Q000737:chemistry* / Q000378:metabolism*; D000693:Anaerobiosis; D001665:Binding Sites; D002244:Carbon / Q000737:chemistry* / Q000378:metabolism*; D008670:Metals / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism
D000085:Acetates; D008670:Metals; D009097:Multienzyme Complexes; D002244:Carbon; D000445:Aldehyde Oxidoreductases; C019823:carbon monoxide dehydrogenase; D010100:Oxygen