title: The metalloclusters of carbon monoxide dehydrogenase/acetyl-CoA synthase: a story in pictures.
abstract: Eight Ni proteins are known and three of these, CO dehydrogenase (CODH), acetyl-CoA synthase (ACS), and hydrogenase, are Ni-Fe-S proteins. In the last three years, the long-awaited structures of CODH and ACS have been solved. The bioinorganic community was shocked, as the structures of the active sites of CODH and ACS, the C- and A-cluster, respectively, which each had been predicted to consist of a [Fe(4)S(4)] cluster bridged to a single Ni, revealed unexpected compositions and arrangements. Crystal structures of ACS revealed major differences in protein conformation and in A-cluster composition; for example, a [Fe(4)S(4)] cluster bridged to a binuclear center in which one of the metal binding sites was occupied by Ni, Cu, or Zn. Recent studies have revealed Ni-Ni to be the active state, unveiled the source of the heterogeneity that had plagued studies of CODH/ACS for decades, and produced a metal-replacement strategy to generate highly active and nearly homogeneous enzyme.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. cdrennan@mit.edu
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Drennan
authors.forename: Tzanko I
authors.initials: TI
authors.lastname: Doukov
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Ragsdale
mesh_terms: D000105:Acetyl Coenzyme A / Q000737:chemistry / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D003300:Copper / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism; D008670:Metals / Q000737:chemistry* / Q000378:metabolism; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism*; D009532:Nickel / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
chemical_list: D007506:Iron-Sulfur Proteins; D008670:Metals; D009097:Multienzyme Complexes; D000105:Acetyl Coenzyme A; D003300:Copper; D009532:Nickel; D000445:Aldehyde Oxidoreductases; C019823:carbon monoxide dehydrogenase; D015032:Zinc