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

Abstract

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 discovered role for copper in biology. The different active sites of this bifunctional enzyme complex are connected via a channel, 138 angstroms long, that provides a conduit for carbon monoxide generated at the C-cluster on one subunit to be incorporated into acetyl-CoA at the A-cluster on the other subunit.

Crystal structure of nickel-containing superoxide dismutase reveals another type of active site

“…Metal coordination by S ligands is a specific feature among known SODs; however, it is not uncommon in Ni-containing enzymes, especially for redox-active enzymes, including [NiFe]-hydrogenase (27), CO dehydrogenase (28), CO dehydrogenase͞ acetyl-CoA synthase (29,30), and methyl coenzyme M reductase (31). Among Ni-containing proteins investigated so far, only redox-active enzymes feature thiolate ligation, which is found neither in the hydrolytically active urease nor in auxiliary proteins for Ni-related cellular tasks.…”

The rocky roots of the acetyl-CoA pathway

“…The structures of a C-cluster in CODH and of the A-cluster of ACS (Figure 2a [16][17][18][19][20]35]. The exact reaction mechanism for ACS has not been resolved: differing proposals have been put forth [17,20] and differences have been also reported regarding the presence of copper, zinc and nickel at the active site of the A cluster [17,20,35]; nickel has been found at the active site of the active enzyme [18]. Only selected metal sulphide centres of CODH and ACS are shown; the protein structure is represented by shading.…”

Synthesis of MFe3S4Clusters Containing a Planar MIISite (M = Ni, Pd, Pt), a Structural Element in the C-Cluster of Carbon Monoxide Dehydrogenase

“…8 Shown in Figure 1 are X-ray structures of three C-clusters from different organisms. All contain a NiFe 4 (μ 3 -S) 4 core with distorted tetrahedral iron sites, among which is an iron atom with apparent Fe(μ 2 -S)(μ 3 -S)(S Cys )(N His ) coordination that is positioned exo to the cubanoid NiFe 3 S 4 portion of the core. The structures differ mainly in the coordination around nickel.…”