A Ni-Fe-Cu Center in a Bifunctional Carbon Monoxide Dehydrogenase/ Acetyl-CoA Synthase

  title={A Ni-Fe-Cu Center in a Bifunctional Carbon Monoxide Dehydrogenase/ Acetyl-CoA Synthase},
  author={Tzanko I. Doukov and Tina M Iverson and Javier Seravalli and Stephen W. Ragsdale and Catherine L. Drennan},
  pages={567 - 572}
A metallocofactor containing iron, sulfur, copper, and nickel has been discovered in the enzyme carbon monoxide dehydrogenase/acetyl-CoA (coenzyme A) synthase from Moorella thermoacetica (f.Clostridium thermoaceticum). Our structure at 2.2 angstrom resolution reveals that the cofactor responsible for the assembly of acetyl-CoA contains a [Fe4S4] cubane bridged to a copper-nickel binuclear site. The presence of these three metals together in one cluster was unanticipated and suggests a newly… 
Acetyl-coenzyme A synthase: the case for a Nip0-based mechanism of catalysis
  • P. Lindahl
  • Chemistry
    JBIC Journal of Biological Inorganic Chemistry
  • 2004
In this review, evidence is presented that Nip achieves a zero-valent state at low potentials and during catalysis, and Ni-organometallic complexes in which the Ni exhibits analogous reactivity properties when reduced to the zero-Valent state are reinforced.
Crystallographic Characterization of the Carbonylated A-Cluster in Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase
Direct structural characterization of CODH/ACS from Moorella thermoacetica with substrate carbon monoxide bound at the A-cluster highlights the role of second sphere residues and conformational dynamics in acetyl-CoA assembly, the biological equivalent of the Monsanto process.
Nickel in subunit beta of the acetyl-CoA decarbonylase/synthase multienzyme complex in methanogens. Catalytic properties and evidence for a binuclear Ni-Ni site.
A mechanism for C-C bond activation is proposed that includes a specific role for the Fe(4)S( 4) center and accounts for the absolute requirement for nickel.
CO Dehydrogenase/Acetyl‐CoA Synthase
The bifunctional tetrameric enzyme carbon monoxide dehydrogenase (CODH)/acetyl-CoA synthase (ACS) undergoes a conformational change that blocks the tunnel near the active site, preventing the escape of the toxic CO from within the enzyme upon methyl binding to nickel.
Redox-dependent rearrangements of the NiFeS cluster of carbon monoxide dehydrogenase
Using X-ray crystallography, unprecedented conformational dynamics in the C-cluster of the CODH from Desulfovibrio vulgaris are observed, providing the first view of an oxidized state of the cluster.
Different modes of carbon monoxide binding to acetyl-CoA synthase and the role of a conserved phenylalanine in the coordination environment of nickel.
A model was developed for how the catalytic properties of the A cluster are optimized by linking conformational changes to a repositionable aromatic shield able to modulate the nucleophilicity of Ni, sterically select the most productive order of substrate addition, and overcome intrinsic inhibition by CO.
Functional copper at the acetyl-CoA synthase active site
Evidence is presented that the copper ion at the M. thermoacetica ACS active site is essential and an essential and functional role for copper in the CODH/ACS from acetogenic and methanogenic organisms.
Ni-Zn-[Fe4-S4] and Ni-Ni-[Fe4-S4] clusters in closed and open α subunits of acetyl-CoA synthase/carbon monoxide dehydrogenase
It is postulate that only the A-clusters containing two Ni ions are catalytically active in the tetrameric α2β2 acetyl-coenzyme A synthase/carbon monoxide dehydrogenase from Moorella thermoacetica.
Targeting synthetic analogues of the metallo-sulfur active sites of nickel enzymes capable of important catalysis
The nickel containing enzymes NiFe-hydrogenase, carbon monoxide dehydrogenase and acetyl-CoA synthase are able to catalyse environmentally, and potentially industrially, important reactions: hydrogen


Crystal Structure of a Carbon Monoxide Dehydrogenase Reveals a [Ni-4Fe-5S] Cluster
This structure represents the prototype for Ni-containing CO dehydrogenases from anaerobic bacteria and archaea and contains five metal clusters of which clusters B, B′, and a subunit-bridging, surface-exposed cluster D are cubane-type [4Fe-4S] clusters.
The Role of an Iron-Sulfur Cluster in an Enzymatic Methylation Reaction
The results described here strongly indicate that transfer of methyl group to carbon monoxide dehydrogenase/acetyl-CoA synthase occurs by an SN2 pathway and support the hypothesis that the [4Fe-4S] cluster of the CFeSP does not participate directly in the methyl transfer step but provides a conduit for electron flow from physiological reductants to the cobalt center.
Life on carbon monoxide: X-ray structure of Rhodospirillum rubrum Ni-Fe-S carbon monoxide dehydrogenase
This x-ray structure of the anaerobic Ni-Fe-S carbon monoxide dehydrogenase (CODH) from Rhodospirillum rubrum provides insight into the mechanism of biological CO oxidation and has broader significance for the roles of Ni and Fe in biological systems.
Nickel-Containing Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase†,‡
This article reviews an enzyme with two important catalytic activities, carbon monoxide dehydrogenase (CODH) (reaction 1) and acetyl-CoA synthase (ACS) (reaction 2). These reactions are key to an
Evidence of a Molecular Tunnel Connecting the Active Sites for CO2 Reduction and Acetyl-CoA Synthesis in Acetyl-CoA Synthase from Clostridium thermoaceticum
Autotrophic bacteria and archaea can grow on CO2 and H2 as their only source of carbon and energy.1 The central enzyme responsible for this process is acetyl-CoA synthase (ACS). ACS from Clostridium
Channeling of carbon monoxide during anaerobic carbon dioxide fixation.
Results provide strong evidence for the existence of a CO channel between cluster C in the CODH subunit and cluster A in the ACS subunit, which would tightly couple CO production and utilization and help explain why high levels of this toxic gas do not escape into the environment.
Rapid kinetic studies of acetyl-CoA synthesis: evidence supporting the catalytic intermediacy of a paramagnetic NiFeC species in the autotrophic Wood-Ljungdahl pathway.
The results indicate that CO inhibits acetyl-CoA synthesis by inhibiting this methyl transfer reaction, which strongly support the kinetic competence of the NiFeC species in the Wood-Ljungdahl pathway.
Spectroscopic, redox, and structural characterization of the Ni-labile and nonlabile forms of the acetyl-CoA synthase active site of carbon monoxide dehydrogenase
The α subunit of carbon monoxide dehydrogenase from Clostridium thermoaceticum was isolated, treated as described below, and examined by XAS, EPR, and UV−vis spectroscopies. This subunit contains the