JBIC Journal of Biological Inorganic Chemistry

, Volume 9, Issue 5, pp 511-515

First online:

The metalloclusters of carbon monoxide dehydrogenase/acetyl-CoA synthase: a story in pictures

  • Catherine L. DrennanAffiliated withDepartment of Chemistry, Massachusetts Institute of Technology Email author 
  • , Tzanko I. DoukovAffiliated withStanford Linear Accelerator Center
  • , Stephen W. RagsdaleAffiliated withDepartment of Biochemistry, Beadle Center, University of Nebraska

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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 [Fe4S4] 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 [Fe4S4] 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.


Acetyl-CoA synthase Carbon monoxide dehydrogenase Iron-sulfur clusters Metalloproteins Nickel