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

  • Catherine L. Drennan
  • Tzanko I. Doukov
  • Stephen W. Ragsdale


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 



corrinoid iron-sulfur protein




carbon monoxide dehydrogenase/acetyl-CoA synthases


electron nuclear double resonance





The authors gratefully acknowledge GM69857 for financial support.


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Copyright information

© SBIC 2004

Authors and Affiliations

  • Catherine L. Drennan
    • 1
  • Tzanko I. Doukov
    • 2
  • Stephen W. Ragsdale
    • 3
  1. 1.Department of ChemistryMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.Stanford Linear Accelerator CenterMenlo ParkUSA
  3. 3.Department of Biochemistry, Beadle CenterUniversity of NebraskaLincolnUSA

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