Structural and spectroscopic models of the A-cluster of acetyl coenzyme a synthase/carbon monoxide dehydrogenase: Nature’s Monsanto acetic acid catalyst

Acetyl coenzyme A synthase/carbon monoxide dehydrogenase (ACS/CODH) is a bifunctional enzyme present in a number of anaerobic bacteria. The enzyme catalyzes two separate reactions namely, the reduction of atmospheric CO2 to CO (CODH activity at the C-cluster) and the synthesis of acetyl coenzyme A (ACS activity at the A-cluster) from CO, CH3 from a corrinoid iron-sulfur protein, and the thiol coenzyme A. The structure(s) of the A-cluster of ACS/CODH from Moorella thermoacetica revealed an unprecedented structure with three different metallic subunits linked to each other through bridging Cys-S residues comprising the active site. In these structure(s) a Fe4S4 cubane is bridged via Cys-S to a bimetallic metal cluster. This bimetallic cluster contains a four-coordinate Ni, Cu, or Zn as the proximal metal (to the Fe4S4 cluster; designated Mp), which in turn is bridged through two Cys-S residues to a terminal square planar Ni(II) (Nid, distal to Fe4S4) ligated by two deprotonated carboxamido nitrogens from the peptide backbone. It is now established that Ni is required at the Mp site for the ACS activity. Over the past several years modeling efforts by several groups have provided clues towards understanding the intrinsic properties of the unique site in ACS. To date most studies have focused on dinuclear compounds that model the Mp–Nid subsite. Synthesis of such models have revealed that the Nip sites (a) are readily removed when mixed with 1,10-phenanthroline (phen) and (b) can be reduced to the Ni(I) and/or Ni(0) oxidation state (deduced by EPR or electrochemical studies) and bind CO in terminal fashion with νco value similar to the enzyme. In contrast, the presence of Cu(I) centers at these Mp sites do not bind CO and are not removable with phen supporting a non-catalytic role for Cu(I) at the Mp site in the enzyme. The Nid site (coordinated by carboxamido-N/thiolato-S) in these models are very stable in the +2 oxidation state and not readily removed upon treatment with phen suggesting that the source of ‘labile Ni’ and the NiFeC ∗ Corresponding author. Tel.: +1 831 459 4251; fax: +1 831 459 2935. E-mail address: [email protected] (P.K. Mascharak). 0010-8545/$ – see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.ccr.2005.04.019 3008 T.C. Harrop, P.K. Mascharak / Coordination Chemistry Reviews 249 (2005) 3007–3024 signal arises from the presence of Ni at the Mp site in ACS. This review includes the results and implications of the modeling studies reported so far. © 2005 Elsevier B.V. All rights reserved.