CO Dehydrogenase/Acetyl-CoA Synthase (CODH/ACS)

Introduction

Every year 1 billion tons of CO are removed from the atmosphere by bacterial oxidation⁷. Carbon Monoxide Dehydrogenase is a bifunctional metalloenzyme belonging to the class of oxidoreductases. The enzyme is also known as Acetyl-CoA Synthase, Carbon Monoxide/Acetyl CoA Synthase and is abbreviated CODH/ACS. There are two types of CODH/ACS: Mo-Fe-Flavin containing enzymes found in aerobic bacteria and Fe-Ni containing enzymes found in anaerobic bacteria, including as methane and sulfur containing bacteria1. The Fe-Ni containing Carbon Monoxide Dehydrogenase is one of only four known nickel containing enzymes⁴. CO Dehydrogenase is important in the global Carbon cycle as well as in the production of acetate in anaerobic bacteria⁵.

Fuction

The enzyme's main function is to catalyze two reactions. The first is an important step in the global Carbon Cycle and involves the conversion of carbon monoxide with water and an electron acceptor substrate to produce carbon dioxide and the reducted acceptor (Figure 1)^1,4,5. Phototrophic anaerobes grow by this process, and it is a very important process for the dark fixation of carbon dioxide into organic matter.⁶ From IR and Raman spectral data it has been suggested that oxidation of CO occurs from Ni-OH attack on Fe-CO and then FeS reduction as CO₂ is released7. The second function is the synthesis of Acetyl-CoA. In this reduced to carbon monoxide from the first reaction is used. The Acetyl-CoA is formed from the reaction of coenzyme A with carbon monoxide and a methyl source (Figure 2).^4,5 This synthesis occurs in acetate-producing autotrophic anaerobes.⁶ The entire process of the reduction of carbon dioxide and the synthesis of Acetyl-CoA is called the Wood Ljundahl Pathway. It is the major CO₂ fixing pathway used by bacteria under anaerobic conditions⁶.

CO + H₂O --> CO₂ + 2 H⁺ + 2 e^-

Figure 1. The overall reaction of the conversion of carbon monoxide to carbon dioxide in the Carbon Cycle catalyzed by CODH/ACS.


CO + CH₃-CFeSP +HSCoA --> CH₃-CO-SCoA + CFeSP + H⁺

Figure 2. The overall reaction of the synthesis of Acetyl-CoA from the reduced carbon monoxide.

Active Sites

Fe-CODH C Cluster

The active site of CODH/ACS contains a [Ni-4Fe-5S] unit known as the C-cluster (figure 3). This C-cluster is the site of the conversion of carbon monoxide to carbon dioxide. The carbon monoxide is then moved through a tunnel in the enzyme to Cluster A. The C-cluster is an asymmetric structure with a C1 point group. The cluster has an unusual coordination structure with the metal centers attached to the peptide backbone by caroxamido nitrogens and Cys-sulfurs. The metal Nickel atom is square planar with four Sulfur ligands attached. The Ni-Ni metal structure belongs to the point group D2h. The C Cluster consists of [Ni-4S-3Fe] cubic structure where each Iron metal ion is bonded to four Sulfur ligands in a tetrahedral geometry. Therefore the Iron metal ions belong to the C3v point group.

Figure 3. [Ni-4Fe-5S] active site unit in CODH/ACS known as the C-cluster.

Fe-CODH A Cluster

The active site on CODH/ACS that catalyzes the synthesis of Acetyl-CoA is referred to as the A Cluster (figure 4). The A cluster consists of a Ni-Ni-4Fe-4S unit attached to a cubic 4s-4Fe cluster by a S-Cys. The cubic 4s-4Fe (figure 5) structure belongs to the Oh point group and is likely to the initial acceptor of electrons from the reduced CODH. The reduced center is also thought to donate electrons to CO 2+.⁶ The Ni-Ni structure bridged together by S-Cys and the remaining coordination sites are filled by additional S-Cys or N/O amino acid residues. The Ni center is the most probable location for the methylation of CODH/ACS. ⁶

^{Figure 4. Cluster A active site of CODH/ACS.}

Figure 5. [4Fe-4S] cubic cluster.

Mo-CODH Structure

The overall structure of the Mo-containing CODH active site is asymmetric (C1 point group) (figure 6). The Molybdenum metal ion center is octahedral with 3 sulfur ions attached and two double bonded oxygen atoms, and on oxygen atom that connects the structure to the peptide backbone. This structure belongs to the D2h point group. The Copper metal ion center is attached to two Sulfur atoms in a bent geometrical arrangement. The structure belongs to the C2v point group.

Figure 6. The structure on the left is of the Molybdenum containing form of Carbon Monoxide Dehydrogenase. The structure on the right is another image of the A Cluster of the Fe-CODH.

Sources

1. Daniel L. Purich and R. Donald Allison. The Enzyme Reference: A comprehenseive guide to Enzyme Nomenclatur, Reactions and Methods. Gainesville, Florida: University of Florida College of Medicine. Department of Biochemistry and Molecular Biology. Academic Press University of Florida College of Medicine. Academic Press. New York. 2002.

2. Thomas G. Spiro. Molybdenum Enzymes. New York: Princeton University, Hon Wiley and Sons New. 1985.

3. Holger Dobbek, Vitali Svetlitchnyi, Jago Liss, and Ortwin Meyer, Carbon Monoxide Induced Decomposition of the Active Site [Ni-4Fe-5S] Cluster of CO Dehydrogenase. Journal of American Cancer Society. 2004, 126, 5382-5287.

4. T. C. Harrop, M. M. Olmstead and P. K. Mascharak, Synthetic Analogues of the Active Site of the A-Cluster of Acetyl Coenzyme A Synthase/CO Dehydrogenase: Syntheses, Structures, and
Reactions with CO. Inorg. Chem. 2006, 45, 3424-3436.

5. T. C. Harrop and P. K. Mascharak, Structural and Spectroscopic Models of the A-Cluster of
Acetyl Coenzyme A Synthase/Carbon Monoxide Dehydrogenase: Nature’s Monsanto Acetic Acid Catalyst. Coord. Chem Rev. 2005, 249, 3007-3024.

6. Ferry, James G. CO Dehydrogenase. Department of Biochemistry, Microbiology, Molecular and Cell Biology. Pennsylvania Sate University. Annu. Rev. Microbiol. 1995, 49, 305-33.

7. Qui, Di Manoj Kumar, Stephen W. Ragsdale, and Thomas G. Spiro, Raman and Infrared Spectroscopy of Cyanide-Inhibited CO Dehydrogenase/Acetyl-CoA Synthase from Clostridium thermoaceticum: Evidence for Bimetallic Enzymatic CO Oxidation. Journal of American Cancer Society. 1996, 118, 10429-10435.