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Acetyl-coenzyme A synthase: the case for a Nip0-based mechanism of catalysis

  • Paul A. LindahlEmail author
Commentary

Abstract

Acetyl-CoA synthase (also known as carbon monoxide dehydrogenase) is a bifunctional Ni-Fe-S-containing enzyme that catalyzes the reversible reduction of CO2 to CO and the synthesis of acetyl-coenzyme A from CO, CoA, and a methyl group donated by a corrinoid iron-sulfur protein. The active site for the latter reaction, called the A-cluster, consists of an Fe4S4 cubane bridged to the proximal Ni site (Nip), which is bridged in turn to the so-called distal Ni site. In this review, evidence is presented that Nip achieves a zero-valent state at low potentials and during catalysis. Nip appears to be the metal to which CO and methyl groups bind and then react to form an acetyl-Nip intermediate. Methyl group binding requires reductive activation, where two electrons reduce some site on the A-cluster. The coordination environment of the distal Ni suggests that it could not be stabilized in redox states lower than 2+. The rate at which the [Fe4S4]2+ cubane is reduced is far slower than that at which reductive activation occurs, suggesting that the cubane is not the site of reduction. An intriguing possibility is that Nip2+ might be reduced to the zero-valent state. Reinforcing this idea are Ni-organometallic complexes in which the Ni exhibits analogous reactivity properties when reduced to the zero-valent state. A zero-valent Ni stabilized exclusively with biological ligands would be remarkable and unprecedented in biology.

Keywords

Carbon monoxide dehydrogenase Nickel(0) Zero-valent nickel 

Notes

Acknowledgements

Many of the developments described here could not have been made without the efforts of Juan C. Fontecilla-Camps and his group in Grenoble. Discussions with Marcetta Y. Darensbourg and Michael B. Hall were critical in developing the Ni0 hypothesis. The author thanks his co-workers at Texas A&M who worked on problems related to this hypothesis over the past decade or so, including Woonsup Shin, David P. Barondeau, Xiangshi Tan, and Matthew R. Bramlett. Thanks are also due to Mark Gerstein and co-workers (Yale University) for preparing the movie of the α subunit conformations. This project is supported by the National Institutes of Health (GM46441).

Supplementary material

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Copyright information

© SBIC 2004

Authors and Affiliations

  1. 1.Departments of Chemistry and of Biochemistry and BiophysicsTexas A&M UniversityCollege StationUSA

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