Carbon monoxide dehydrogenase structure

Figure 4.17 Schematic structures for the active site of carbon monoxide dehydrogenase. Structure a shows that initially proposed from protein crystallography and h shows the final structure, based on improved crystallography and XAS.

Dobbek H, V Svetlitchnyi, L Gremer, R Huber, O Meyer (2001) Crystal structure of a carbon monoxide dehydrogenase reveals a [Ni-4Fe-5S] cluster. Science 293 1281-1285. 

Drennan CL, J Heo, MD Sintchak, E Schreiter, PW Ludden (2001) Life on carbon monoxide x-ray structure of Rhodospirillum rubrum Ni-Fe-S carbon monoxide dehydrogenase. Proc Natl Acad Sci USA 98 11973-11978. 

Figure 2 Structures of the actrive sites of metalloenzymes containing metal-sulfur cluster units, (a) Fe only hydrogenase, H-cluster (Hoxfarm) (b) Sulfite reductase (c) NiFe carbon monoxide dehydrogenase, C-cluster and (d) NiFe carbon monoxide dehydrogenase, A-cluster, which functions as acetyl-CoA synthase...

The molybdenum-containing enzymes considered in Section F also contain Fe-S clusters. Nitrogenases (Chapter 24) contain a more complex Fe-S-Mo cluster. Carbon monoxide dehydrogenase (Section C) contains 2 Ni, 11 Fe, and 14 S2 as well as Zn in a dimeric structure. In these enzymes the Fe-S clusters appear to participate in catalysis by undergoing alternate reduction and oxidation. 

Iron Sulfur Compounds. Many molecular compounds (18—20) are known in which iron is tetrahedrally coordinated by a combination of thiolate and sulfide donors. Of the 10 or more structurally characterized classes of Fe—S compounds, the four shown in Figure 1 are known to occur in proteins. The mononuclear iron site REPLACE occurs in the one-iron bacterial electron-transfer protein rubredoxin. The [2Fe—2S] (10) and [4Fe—4S] (12) cubane structures are found in the 2-, 4-, and 8-iron ferredoxins, which are also electron-transfer proteins. The [3Fe—4S] voided cubane structure (11) has been found in some ferredoxins and in the inactive form of aconitase, the enzyme which catalyzes the stereospecific hydration—rehydration of citrate to isocitrate in the Krebs cycle. In addition, enzymes are known that contain either other types of iron sulfur clusters or iron sulfur clusters that include other metals. Examples include nitrogenase, which reduces N2 to NH3 at a MoFe S8 homocitrate cluster carbon monoxide dehydrogenase, which assembles acetyl-coenzyme A (acetyl-CoA) at a FeNiS site and hydrogenases, which catalyze the reversible reduction of protons to hydrogen gas. 

Smith MC, Barclay JE, Cramer SP, Davies SC, Gu W-W, Hughes DL, Longhurst S, Evans DJ (2002) Nickel-iron-sulfur complexes approaching structural analogues of the active sites of NiFe-hydrogenase and carbon monoxide dehydrogenase/acetyl-CoA synthase. Dalton Trans. 2641-2647... 

There are now three different proteins of the XDH/XO family whose structures have been determined by X-ray protein crystallography. The structure of aldehyde oxidoreductase from the bacterium Desulfovibrio gigas was the first X-ray structure determined for an oxo-molybdenum enzyme (17) and has been followed by stmctures of XO/XDH (10) and carbon monoxide dehydrogenase (CODH) (19, 21). Although the three enzymes are placed in the same family, there are structural differences among them at the active site and at the phosphate remote from the Mo center. 

Russell, W. K., Stalhmidske, C. M. V., Xia, J. Q., Scott, R. A., and Lindahl, P. A., 1998, Spech o-scopic, redox, and structural characterization of die Ni-labile and nonlabile forms of the acetyl-CoA synthase active. Site of carbon monoxide dehydrogenase, J. Am. Chem. Soc. 120(30) 7502n7510. 

The active site of carbon monoxide dehydrogenase has been shown to contain an asymmetric [Ni-4Fe-5S] cluster. There have been two recent independent reports of X-ray structures for the bifunctional enzyme carbon monoxide dehydrogenase/acetyl-coenzyme A synthase. In both structures, Ni is also bound in the acetyl-coenzyme A synthase within a N2S2 environment originating from amide N- and thiolate S-donors. The latter donors bridge to either a Cu, Zn, or Ni, which in turn is connected to a 4Fe4S cluster. ... 

For example, incorporation of nickel into carbon monoxide dehydrogenase of Rhodospirillum rubrum requires the prior reduction of an Fe-S cluster. Structural studies of this protein reveal that the added Ni completes a unique [lNi-4Fe-4S] center that is required for activity.Another example of a reductive activation step occurs during NiFe-hydrogenase biosynthesis, perhaps involving participation of the Fe-S cluster in HypD. Yet a third example from the Ni-enzyme literature involves the synthesis of methyl-X-coenzyme M reductase, a methanogen enzyme that contains the Ni-tetrapyrrole cofactor F43q. Formation of active enzyme requires both the reduction of Ni + to NF+ and reduction of a C=N bond in the organic macrocycle. 

Figure 5 Structures of the (a) Fe3S4(Cys)4 ferredoxin site (PDB 7FD1) (b) aconitase active site with bound trans-aconitate (PDB lACO) (c) NiFe4Ss cluster in carbon monoxide dehydrogenase (PDB IJQK).

Structural and spectroscopic models of the A-cluster of acetyl coenzyme A synthase/carbon monoxide dehydrogenase 05CCR(249)3007. 

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