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

• Published in: Coordination chemistry reviews 2005-12, Vol.249 (24), p.3007-3024
• Main Authors: Harrop, Todd C., Mascharak, Pradip K.
• Format: Article
• Language: English
• Subjects: A-cluster; Acetyl coenzyme A synthase; CO binding; Model complexes
• ISSN: 0010-8545; 1873-3840
• DOI: 10.1016/j.ccr.2005.04.019

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 CO 2 to CO (CODH activity at the C-cluster) and the synthesis of acetyl coenzyme A (ACS activity at the A-cluster) from CO, CH 3 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 Fe 4S 4 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 Fe 4S 4 cluster; designated M p), which in turn is bridged through two Cys-S residues to a terminal square planar Ni(II) (Ni d, distal to Fe 4S 4) ligated by two deprotonated carboxamido nitrogens from the peptide backbone. It is now established that Ni is required at the M p 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 M p–Ni d subsite. Synthesis of such models have revealed that the Ni p 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 ν co value similar to the enzyme. In contrast, the presence of Cu(I) centers at these M p sites do not bind CO and are not removable with phen supporting a non-catalytic role for Cu(I) at the M p site in the enzyme. The Ni d 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 signal arises from the presence of Ni at the M p site in ACS. This review includes the results and implications of the modeling studies reported so far.