Binding of carbon disulfide to the site of acetyl-CoA synthesis by the nickel-iron-sulfur protein, carbon monoxide dehydrogenase, from Clostridium thermoaceticum. 1994

M Kumar, and W P Lu, and S W Ragsdale
Department of Biochemistry, University of Nebraska, Lincoln 68583-0718.

Carbon monoxide dehydrogenase (CODH) is a key enzyme in the pathway of carbon monoxide and carbon dioxide fixation by anaerobic bacteria. It performs the oxidation of CO to CO2, the reduction of CO2 to CO, and the synthesis of acetyl-CoA from a methylated corrinoid/iron-sulfur protein, CO, and CoA. These reactions occur at metal centers on CODH and involve metal-carbon bond formation and transformation. There are three iron-containing centers that play distinct roles in CODH: Centers A, B, and C. Center A is the site of synthesis of acetyl-CoA and catalyzes an exchange reaction between CO and acetyl-CoA. Center C is the site of CO oxidation and CO2 reduction. In the work described here, inhibition of CODH by carbon disulfide was studied. CS2 was found to serve as a probe of the interaction of CODH with CO at Center A. EPR spectroscopic and steady-state kinetic studies demonstrated that CS2 mimics the binding of CO to the nickel/iron-sulfur cluster at Center A; however, CS2 itself does not undergo oxidation-reduction and does not appear to bind to Center C as does CO. In the isotope exchange reaction between acetyl-CoA and CO, CS2 was found to be a competitive inhibitor with respect to CO (Ki = 0.47 mM) and a mixed inhibitor with respect to acetyl-CoA (Ki1 = 0.30 and Ki2 = 1.1 mM). The reaction of dithionite-reduced CODH with CS2 resulted in an EPR spectrum with g values of 2,200, 2,087, and 2,017.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007506 Iron-Sulfur Proteins A group of proteins possessing only the iron-sulfur complex as the prosthetic group. These proteins participate in all major pathways of electron transport: photosynthesis, respiration, hydroxylation and bacterial hydrogen and nitrogen fixation. Iron-Sulfur Protein,Iron Sulfur Proteins,Iron Sulfur Protein,Protein, Iron-Sulfur,Proteins, Iron Sulfur,Proteins, Iron-Sulfur,Sulfur Proteins, Iron
D008667 Metalloproteins Proteins that have one or more tightly bound metal ions forming part of their structure. (Dorland, 28th ed) Metalloprotein
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009097 Multienzyme Complexes Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES. Complexes, Multienzyme
D009532 Nickel A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme UREASE.
D002245 Carbon Dioxide A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. Carbonic Anhydride,Anhydride, Carbonic,Dioxide, Carbon
D002246 Carbon Disulfide A colorless, flammable, poisonous liquid, CS2. It is used as a solvent, and is a counterirritant and has local anesthetic properties but is not used as such. It is highly toxic with pronounced CNS, hematologic, and dermatologic effects. Disulfide, Carbon
D002248 Carbon Monoxide Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. (From Merck Index, 11th ed) Monoxide, Carbon
D003013 Clostridium A genus of motile or nonmotile gram-positive bacteria of the family Clostridiaceae. Many species have been identified with some being pathogenic. They occur in water, soil, and in the intestinal tract of humans and lower animals.
D004578 Electron Spin Resonance Spectroscopy A technique applicable to the wide variety of substances which exhibit paramagnetism because of the magnetic moments of unpaired electrons. The spectra are useful for detection and identification, for determination of electron structure, for study of interactions between molecules, and for measurement of nuclear spins and moments. (From McGraw-Hill Encyclopedia of Science and Technology, 7th edition) Electron nuclear double resonance (ENDOR) spectroscopy is a variant of the technique which can give enhanced resolution. Electron spin resonance analysis can now be used in vivo, including imaging applications such as MAGNETIC RESONANCE IMAGING. ENDOR,Electron Nuclear Double Resonance,Electron Paramagnetic Resonance,Paramagnetic Resonance,Electron Spin Resonance,Paramagnetic Resonance, Electron,Resonance, Electron Paramagnetic,Resonance, Electron Spin,Resonance, Paramagnetic

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