In enzymology, carbon monoxide dehydrogenase is an enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 that catalyzes

Catalysis

Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....

 the chemical reaction

Chemical reaction

A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...

CO + H₂O + A CO₂ + AH₂

The 3 substrates

Substrate (biochemistry)

In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...

 of this enzyme are CO

Carbon monoxide

Carbon monoxide , also called carbonous oxide, is a colorless, odorless, and tasteless gas that is slightly lighter than air. It is highly toxic to humans and animals in higher quantities, although it is also produced in normal animal metabolism in low quantities, and is thought to have some normal...

, H₂O

Water

Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...

, and A, whereas its two products

Product (chemistry)

Product are formed during chemical reactions as reagents are consumed. Products have lower energy than the reagents and are produced during the reaction according to the second law of thermodynamics. The released energy comes from changes in chemical bonds between atoms in reagent molecules and...

 are CO₂

Carbon dioxide

Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...

 and AH₂.

This enzyme belongs to the family of oxidoreductase

Oxidoreductase

In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule to another...

s, specifically those acting on the aldehyde or oxo group of donor with other acceptors. The systematic name of this enzyme class is carbon-monoxide:acceptor oxidoreductase. Other names in common use include anaerobic carbon monoxide dehydrogenase, carbon monoxide oxygenase, carbon-monoxide dehydrogenase, and carbon-monoxide:(acceptor) oxidoreductase.

Classes

Two major classes of the carbon monoxide dehydrogenase (CODH) enzymes have been identified. CODH containing a Mo-[2Fe-2S]-FAD active site have been found in aerobic bacteria, while a distinct class of Ni-[3Fe-4S] CODH enzymes have been purified from anaerobic bacteria. Both classes of CODH catalyze the reversible conversion between carbon dioxide (CO₂) and carbonmonoxide (CO). CODH exists in both monofuctional and bifunctional forms. In the latter case, CODH forms a bifunctional cluster with acetyl-CoA synthase, as has been well characterized in the anaerobic bacteria Moorella thermoacetica.

Structure

Multiple research groups have proposed crystal structures for the α₂β₂ tetrameric enzyme CODH/ACS from the acetogenic bacteria M. thermoacetica, including two recent examples since 2009: . The two β units are the site of CODH activity and form the central core of the enzyme. In total, the 310 kDa enzyme contains seven iron-sulfur [4Fe-4S] clusters. Each α unit contains a single metal cluster. Together, the two β units contains five clusters of three types. CODH catalytic activity occurs at the Ni-[3Fe-4S] C-clusters while the interior [4Fe-4S] B and D clusters transfer electrons away form the C-cluster to external electron carriers such as ferredoxin

Ferredoxin

Ferredoxins are iron-sulfur proteins that mediate electron transfer in a range of metabolic reactions. The term "ferredoxin" was coined by D.C. Wharton of the DuPont Co...

. The ACS activity occurs in A-cluster located in the outer two α units.

A noteworthy feature of the M.thermoacetica CODH/ACS is an internal gas tunnel connecting the multiple active sites. The full role of the gas channel in regulating the rate catalytic activity is still a subject of investigation, but several studies support the notion that molecules of CO do in fact travel directly from the C-cluster to the ACS active site without leaving the enzyme. For instance, the rate of acetyl-CoA synthase activity in the bifunctional enzyme is not affected by the addition of hemoglobin, which would compete for CO in bulk solution, and isotopic labeling studies show that carbon monoxide derived from the C-cluster is preferentially used at the A-cluster over unlabeled CO in solution. Protein engineering of the CODH/ACS in M.thermoacetica revealed that mutating residues, so as to functionally block the tunnel, stopped acety-CoA synthesis when only CO₂ was present.
The discovery of a functional CO tunnel places CODH on a growing list of enzymes that independently evolved this strategy to transfer reactive intermediates from one active site to another.

As of late 2007, 13 structures

Tertiary structure

In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...

 have been solved for this class of enzymes, with PDB

Protein Data Bank

The Protein Data Bank is a repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids....

 accession codes , , , , , , , , , , , , and .

Oxidative mechanism

The CODH catalytic site, referred to as the C-cluster, is a [3Fe-4S] cluster bonded to a Ni-Fe moiety. Two basic amino acids (Lys587 and His 113 in M.thermoacetica) reside in proximity to the C-cluster and facilitate acid-base chemistry required for enzyme activity. Based on IR spectra suggesting the presence of an Ni-Co complex, the proposed first step in the oxidative catalysis of CO to CO₂involves the binding of CO to Ni²⁺ and corresponding complexing of Fe²⁺ to a water molecule. The binding of CO molecule causes a shift in the coordination of the Ni atom from a square-planar to square pyramidal geometry. Dobbek et al. further propose that movement of the Nickel atom’s cysteine ligand brings the CO into close proximity to the hydroxyl group, and facilitate a base-catalyzed, nucleophillic attack by the iron-bound hydroxy group. A carboxy bridge between the Ni and Fe atom has been proposed as an intermediate.
A decarboxylation leads to the release of CO₂ and the reduction of the cluster. Although the resulting intermediate oxidation state of the Ni and the degree to which electrons are distributed throughout the Ni-[3Fe-4S] cluster is subject of some debate, the electrons in the reduced C-cluster are transferred to nearby B and D [4Fe-4S] clusters, returning the Ni-[3Fe-4S] C-cluster to an oxidized state and reducing the single electron carrier ferredoxin

Ferredoxin

Ferredoxins are iron-sulfur proteins that mediate electron transfer in a range of metabolic reactions. The term "ferredoxin" was coined by D.C. Wharton of the DuPont Co...

.

Reductive mechanism

Given CODH's role in CO₂ fixation identified in diverse autotrophic bacteria and archaea, it is common in the biochemistry literature for the reductive mechanism to be inferred as the “direct reverse” of the oxidative mechanism by the ”principal of microreversibility.” In the process of reducing carbon dioxide, the enzyme's C-cluster must first be activated from an oxidized to a reduced state before the Ni-CO₂ bond is formed.

Biological function

Carbon monoxide dehydrogenase participates in diverse prokaryotic biochemical pathways, including the metabolism of methanogenic, aerobic carboxidotrophic, acetogenic bacteria, sulfate-reducing, and hydrogenogenic bacteria. The bidirectional reaction catalyzed by CODH play a role in the carbon cycle allowing organisms to both make use of CO as a source of energy and utilize CO₂ as a source of carbon. CODH can form a monofunctional enzyme, as is the case in Rhodospirillum rubram, or can form a cluster with acetyl-CoA synthase as has been shown in M.thermoacetica. When acting in concert, either as structurally independent enzymes or in a bifunctional CODH/ACS unit, the two catalytic sites are key to carbon fixation in the reductive acetyl-CoA pathway

Reductive acetyl-CoA pathway

The Wood–Ljungdahl pathway is a set of biochemical reactions used by some bacteria and archaea. It is also known as the reductive acetyl–CoA pathway...

.

Environmental relevance

CODH is important for maintaining current atmospheric conditions. Microbial metabolisms of CO maintains ambient CO at levels safe for other forms of life.