Carbon monoxide dehydrogenase

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carbon-monoxide dehydrogenase (acceptor)
Identifiers
EC number 1.2.99.2
CAS number 64972-88-9
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

In enzymology, carbon monoxide dehydrogenase (EC 1.2.99.2) is an enzyme that catalyzes the chemical reaction

CO + H2O + A \rightleftharpoons CO2 + AH2

The 3 substrates of this enzyme are CO, H2O, and A, whereas its two products are CO2 and AH2.

This enzyme belongs to the family of oxidoreductases, 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[edit]

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.[1][2] 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.[3][4]

Structure[edit]

Structure of CODH/ACS in M.thermoacetica." Alpha (ACS) and beta (CODH) subunits are shown. (1)The A-cluster Ni-[4Fe-4S]. (2)C-cluster Ni-[3Fe-4S]. (3) B-Cluster [4Fe-4S]. (4) D-cluster [4Fe-4S]. Designed from 3I01

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: 3I01 2Z8Y. 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 from the C-cluster to external electron carriers such as ferredoxin. The ACS activity occurs in A-cluster located in the outer two α units.[1][2]

A noteworthy feature of the M.thermoacetica CODH/ACS is an internal gas tunnel connecting the multiple active sites.[5] 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,[6] 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.[7] 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.[8] 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.[9]

As of late 2007, 13 structures have been solved for this class of enzymes, with PDB accession codes 1JQK, 1MJG, 1N5W, 1N60, 1N61, 1N62, 1N63, 1OAO, 1SU6, 1SU7, 1SU8, 1SUF, and 1ZXI.

Reaction mechanisms[edit]

Oxidative mechanism[edit]

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.[10] Based on IR spectra suggesting the presence of an Ni-CO complex, the proposed first step in the oxidative catalysis of CO to CO2 involves the binding of CO to Ni2+ and corresponding complexing of Fe2+ to a water molecule.[11] The binding of CO molecule causes a shift in the coordination of the Ni atom from a square-planar to square pyramidal geometry.[12] 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. [13] 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.[14]

Reductive mechanism[edit]

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.”[15] 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.[16]

Biological function[edit]

Carbon monoxide dehydrogenase participates in diverse prokaryotic biochemical pathways, including the metabolism of methanogenic, aerobic carboxidotrophic, acetogenic bacteria, sulfate-reducing, and hydrogenogenic bacteria.[1] The bidirectional reaction catalyzed by CODH plays 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.[17]

Environmental relevance[edit]

CODH is important for maintaining current atmospheric conditions. Microbial metabolism of CO maintains ambient CO at levels safe for other forms of life.[18]

References[edit]

  1. ^ a b c Dobbek H, Svetlitchnyi V, Gremer L, Huber R, Meyer O (August 2001). "Crystal structure of a carbon monoxide dehydrogenase reveals a [Ni-4Fe-5S] cluster". Science 293 (5533): 1281–5. doi:10.1126/science.1061500. PMID 11509720. 
  2. ^ a b Lindahl PA (2009). "Nickel-Carbon Bonds in Acetyl-Coenzyme A Synthases/Carbon Monoxide Dehydrogenases". In Sigel, Helmut; Sigel, Astrid. Metal-Carbon Bonds in Enzymes and Cofactors (Metal Ions in Life Sciences). Cambridge, Eng: Royal Society of Chemistry. doi:10.1039/9781847559333. ISBN 1-84755-915-8. 
  3. ^ Doukov TI, Blasiak LC, Seravalli J, Ragsdale SW, Drennan CL (March 2008). "Xenon in and at the end of the tunnel of bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase". Biochemistry 47 (11): 3474–83. doi:10.1021/bi702386t. PMID 18293927. 
  4. ^ Tan X, Volbeda A, Fontecilla-Camps JC, Lindahl PA (April 2006). "Function of the tunnel in acetylcoenzyme A synthase/carbon monoxide dehydrogenase". J. Biol. Inorg. Chem. 11 (3): 371–8. doi:10.1007/s00775-006-0086-9. PMID 16502006. 
  5. ^ Doukov TI, Blasiak LC, Seravalli J, Ragsdale SW, Drennan CL (March 2008). "Xenon in and at the end of the tunnel of bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase". Biochemistry 47 (11): 3474–83. doi:10.1021/bi702386t. PMID 18293927. 
  6. ^ Doukov, T.I.; Iverson, T.M.; Seravalli, J.; Ragsdale, S.W.; Drennan, C.L. (2002), "A Ni-Fe-Cu center in a bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase", Science 298 (5593): 567, doi:10.1126/science.1075843, PMID 12386327 
  7. ^ Seravalli, J.; Ragsdale, S.W. (2000), "Channeling of Carbon Monoxide during Anaerobic Carbon Dioxide Fixation", Biochemistry 39 (6): 1274–1277, doi:10.1021/bi991812e, PMID 10684606 
  8. ^ Tan, X.; Loke, H.K.; Fitch, S.; Lindahl, P.A. (2005), "The tunnel of acetyl-coenzyme a synthase/carbon monoxide dehydrogenase regulates delivery of CO to the active site", Journal of the American Chemical Society 127 (16): 5833–5839, doi:10.1021/ja043701v, PMID 15839681 
  9. ^ Weeks, A.; Lund, L.; Raushel, F.M. (2006), "Tunneling of intermediates in enzyme-catalyzed reactions", Current Opinion in Chemical Biology 10 (5): 465–472, doi:10.1016/j.cbpa.2006.08.008, PMID 16931112 
  10. ^ Ragsdale SW (August 2006). "Metals and their scaffolds to promote difficult enzymatic reactions". Chem. Rev. 106 (8): 3317–37. doi:10.1021/cr0503153. PMID 16895330. 
  11. ^ Chen, J.; Huang, S.; Seravalli, J.; Gutzman Jr, H.; Swartz, D.J.; Ragsdale, S.W.; Bagley, K.A. (2003), "Infrared Studies of Carbon Monoxide Binding to Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase from Moorella thermoacetica%u2020", Biochemistry 42 (50): 14822–14830, doi:10.1021/bi0349470, PMID 14674756 
  12. ^ Dobbek, H.; Svetlitchnyi, V.; Gremer, L.; Huber, R.; Meyer, O. (2001), "Crystal structure of a carbon monoxide dehydrogenase reveals a [Ni-4Fe-5S] cluster", Science 293 (5533): 1281, doi:10.1126/science.1061500, PMID 11509720 
  13. ^ Ha, Seung-Wook; Korbas, Malgorzata; Klepsch, Mirjam; Meyer-klaucke, Wolfram; Meyer, Ortwin; Svetlitchnyi, Vitali (2007), "Interaction of Potassium Cyanide with the [Ni-4Fe-5S] Active Site Cluster of CO Dehydrogenase from Carboxydothermus", Journal of Biological Chemistry 14 (282): 10639–10646, doi:10.1074/jbc.M610641200 
  14. ^ Ragsdale, S.W., "Nickel and the carbon cycle", J Inorg Biochem. 101 (Nov): 1657–66, doi:10.1016/j.jinorgbio.2007.07.014, PMC 2100024, PMID 17716738 
  15. ^ Ragsdale SW, Pierce E (December 2008). "Acetogenesis and the Wood-Ljungdahl pathway of CO(2) fixation". Biochim. Biophys. Acta 1784 (12): 1873–98. doi:10.1016/j.bbapap.2008.08.012. PMC 2646786. PMID 18801467. 
  16. ^ Feng J, Lindahl PA (February 2004). "Carbon monoxide dehydrogenase from Rhodospirillum rubrum: effect of redox potential on catalysis". Biochemistry 43 (6): 1552–9. doi:10.1021/bi0357199. PMID 14769031. 
  17. ^ Hegg EL (October 2004). "Unraveling the structure and mechanism of acetyl-coenzyme A synthase". Acc. Chem. Res. 37 (10): 775–83. doi:10.1021/ar040002e. PMID 15491124. 
  18. ^ Bartholomew, G.W.; Alexander, M. (1979), "Microbial metabolism of carbon monoxide in culture and in soil", Applied and Environmental Microbiology 37 (5): 932, retrieved 2010-05-15 

Further reading[edit]

  • Drennan CL, Heo J, Sintchak MD, Schreiter E, Ludden PW (2001). "Life on carbon monoxide: X-ray structure of Rhodospirillum rubrum Ni-Fe-S carbon monoxide dehydrogenase". Proc. Natl. Acad. Sci. U.S.A. 98: 11973–8. doi:10.1073/pnas.211429998. PMID 11593006.