Stephen Ragsdale, Ph.D.

David Ballou Collegiate Professor, Biological Chemistry

Ofc: 5220D MSRB III

1150 W. Medical Center Drive

Ann Arbor, MI  48109-5606

 

(734) 615-4621

Appointments

Biological Chemistry, Medical School

Areas of Interest

The students and postdoctors in my laboratory work at the interfaces between chemistry, biology, and physics and are studying processes that are important in the global carbon cycle, basic energy sciences, and in biomedical problems. We focus on three major areas: microbial metabolism of one-carbon compounds (CO, CO₂, methane); the roles of metal ions in biology (including the mechanisms of nickel, B12, heme, and iron-sulfur enzymes); the regulation of metabolism and protein function by heme, CO, and thiol-disulfide redox switches. Techniques that we use in addressing research questions in these areas include transient and steady-state kinetics, spectroscopy, cell biology, genetics and molecular biology. The research is funded by NIH and DOE.

Microbial Methane Biosynthesis: Methanogens are masters at carbon dioxide reduction and the key enzyme in their metabolism is methyl coenzyme M reductase (MCR), which contains a nickel tetrapyrrolic cofactor. MCR is responsible for over 90 percent of all biologically generated methane on Earth. Based on recent studies in which we trapped intermediates in the MCR reaction mechanism and characterized them by spectroscopic and crystallographic methods, our work has revealed a mechanism for methane synthesis involving methyl radical intermediate.

Microbial CO₂ and CO Metabolism: Anaerobic CO and CO₂ metabolism play key roles in the global carbon cycle. We are characterizing a nickel-iron-sulfur (NiFeS) bifunctional protein complex called CO dehydrogenase/acetyl-CoA synthase (CODH/ACS) that is the central enzyme in the Wood-Ljungdahl pathway of anaerobic CO₂ fixation. CODH/ACS enables microbial growth on CO₂ and the toxic gas CO. In this complex, CODH reduces CO₂ to CO, which migrates from the NiFeS active site of CODH through a 70 Å tunnel to the NiFeS active site of ACS, which catalyzes acetyl-CoA synthesis from CO, a methyl group (donated by a B12 containing enzyme), and CoA. We also are studying radical chemistry and methyl and proton transfer in a methyltransferase, a vitamin B12/iron-sulfur protein, and pyruvate ferredoxin oxidoreductase, which play key roles in this important component of the carbon cycle.

Oxygen Sensing and Thiol-Disulfide Regulation: We have discovered a mode of metabolic regulation in which thiol/disulfide redox switches control the function of diverse proteins through regulating their affinity for heme and CO. For example, we identified and characterized a redox switch in human heme oxygenase-2 (HO2), which plays an important role in heme homeostasis and in generating CO, a signal molecule that regulates many physiological processes. We also have recently uncovered thiol/disulfide redox switches that regulate heme and CO binding to a potassium channel (BK channel) that interacts with HO2 and is involved in regulating oxygen levels in the blood stream and a key transcriptional regulator of the circadian cycle (RevErb). Various in vivo and in vitro approaches are being used to study how redox and ligand (heme, CO, NO) binding regulate activity, protein-protein interactions and downstream metabolic events involving HO2, the BK channel, RevErb and related systems.

Microbial Mercury Methylation: In collaboration with the Mercury Science Focus Area at Oak Ridge National Laboratory (ORNL) , we are studying the enzymes involved in methylation of mercury. Methylmercury (MeHg) is a neurotoxin and widespread environmental pollutant with no known biological function. Anaerobic microorganisms produce this highly toxic compound by methylating less toxic inorganic mercury (Hg) species in the environment, but the biosynthetic pathway by which this occurs is unknown. We are studying HgcA, a membrane-associated cobalamin-containing protein and HgcB, a soluble iron-sulfur protein.

Program Affiliations

Chemical Biology Doctoral Program
Cellular and Molecular Biology Program
Chemical Biology Interface Training Program
University of Michigan Energy Institute
Graham Sustainability Institute

Funding & Collaborations

Ragsdale Lab Funding
Ragsdale Lab Collaborators

Teaching

Recent Courses
Creativity in the Sciences and Arts course featured in ASBMB Today
Enzyme Purification Blues music video on ASBMB Today's YouTube channel

Scientific Outreach

Co-organizer of Abacus and Rose: SciArt Live, a science-art discussion series with the inaugural performance “Earth Without Ice” held at the Kerrytown Concert House in Ann Arbor, MI, October 2012

"Steve the Science Guy" biweekly science series at the Ozone House in Ann Arbor, MI

Honors & Awards

2018   Distinguished Faculty Achievement Award, University of Michigan
2016   Endowment for Basic Sciences Recognition Award, University of Michigan
2015   David Ballou Collegiate Professorship, University of Michigan
2013   Inducted into University of Michigan League of Education Excellence
2012   National Institutes of Health MERIT Award
2011, 2012   Finalist, Provost's Teaching Innovation Prize
2011   Inducted into University of Michigan League of Research Excellence
2009   Frederick J. Bollum Endowed Biochemistry Lectureship, University of Minnesota
2009   Ljungdahl Lectureship, University of Georgia, Athens, GA
2009   Elected Fellow, American Association for the Advance of Science
2006   Elected Fellow, American Academy of Microbiology
2003   Charles E. Bessey Professorship, University of Nebraska
2003   Outstanding Research and Creativity Award, University of Nebraska
1987-1992   Shaw Scholar Award, Milwaukee Foundation
1985-1986   Public Health Service National Research Service Award, National Institutes of Health
 

Editorial Boards

2017-2022      The Journal of Biological Chemistry (also 1997-2002, 2003-2008 & 2012-2017)
2011-present   Frontiers in Microbiological Chemistry
2006-present   Current Opinions in Chemical Biology
1987-2016       Biofactors
2007-2010       BBA Proteins and Proteomics
1996-2004       Journal of Bacteriology
2003-2006       Archives of Microbiology
1999-2002       Archives of Biochemistry and Biophysics

Credentials

Published Articles or Reviews

2017-2018

Production and properties of enzymes that activate and produce carbon monoxide.
Burton R, Can M, Esckilsen D, Wiley S, Ragsdale SW.
Methods Enzymol. 2018; 613: 297-324.

An unlikely heme chaperone confirmed at last.
Fleischhacker AS, Ragsdale SW.
J Biol Chem. 2018; 293: 14569-70.

Binding site for coenzyme A revealed in the structure of pyruvate:ferredoxin oxidoreductase from Moorella thermoacetica.
Chen PY, Aman H, Can M, Ragsdale SW, Drennan CL.
Proc Natl Acad Sci U S A. 2018; 115: 3846-51.

Fast and Selective Photoreduction of CO2 to CO catalyzed by a Complex of Carbon Monoxide Dehydrogenase, TiO2 and Ag Nanoclusters.
Zhang L, Can M, Ragsdale SW, Armstrong, F. 
ACS Catal. 2018; 82789−95.

Stealth reactions driving carbon fixation.
Ragsdale SW.
Science. 2018; 359: 517-18.

Redox Regulation of Heme Oxygenase-2 and the Transcription Factor, Rev-Erb, Through Heme Regulatory Motifs.
Fleischhacker AS, Carter EL, Ragsdale SW.
Antioxid Redox Signal. 2018; 29: 1841-57.

Properties of Intermediates in the Catalytic Cycle of Oxalate Oxidoreductase and Its Suicide Inactivation by Pyruvate.
Pierce E, Mansoorabadi SO, Can M, Reed GH, Ragsdale SW.
Biochemistry. 2017; 56: 2824-35.

The heme-regulatory motif of nuclear receptor Rev-erbβ is a key mediator of heme and redox signaling in circadian rhythm maintenance and metabolism.
Carter EL, Ramirez Y, Ragsdale SW.
J Biol Chem. 2017; 292: 11280-99.

X-ray Absorption Spectroscopy Reveals an Organometallic Ni-C Bond in the CO-Treated Form of Acetyl-CoA Synthase.
Can M, Giles LJ, Ragsdale SW, Sarangi R.
Biochemistry. 2017; 56: 1248-60.

Biochemistry of Methyl-Coenzyme M Reductase.
Ragsdale SW, Raugei S, Ginovska B, Wongnate T.
In The Biological Chemistry of Nickel (Royal Society of Chemistry). 2017; Ch. 8: 149-69.

2015-2016

Naw May Pearl, Jarett Wilcoxen, Sangchoul Im, Ryan Kunz, Joseph Darty, R. David Britt, Stephen W. Ragsdale, Lucy Waskell (2016) Protonation of the hydroperoxo intermediate of cytochrome P450 2B4 is slower in the presence of cytochrome P450 reductase than in the presence of cytochrome b5. Biochemistry 55, 6558-67.

Richards,M.A., Lie, T.J., Zhang, J., Ragsdale, S.W., Leigh, J.A., John, Price, N.D. (2016) Exploring Hydrogenotrophic Methanogenesis: A Genome Scale Metabolic Reconstruction of Methanococcus maripaludis, J Bacteriol 198, 3379-90. PMC5116941.

Ragsdale, S. W. (2016) Microbiology: Deep-sea secrets of butane metabolism, Nature 539, 367-8.

Ragsdale, S. W. (2016) Targeting Methanogenesis with a Nitrooxypropanol Bullet Proc. Natl. Acad. Sci. U.S.A.113, 6100-1.  PMC4896677.

Wongnate, T., Sliwa, D., Ginovska, B., Smith, D., Wolf, M. W., Lehnert, N., Raugei, S., and Ragsdale, S.W. (2016)The Radical Mechanism of Biological Methane Synthesis by Methyl-Coenzyme M Reductase, Science 352, 953-958. Abstract, Reprint, Full Text.

Carter, E. L., Gupta, N., and Ragsdale, S. W. (2016) High Affinity Heme Binding to a Heme Regulatory Motif on the Nuclear Receptor Rev-erbβ Leads to its Degradation and Indirectly Regulates its Interaction with Nuclear Receptor Corepressor J. Biol. Chem. 291: 2196-2222. PMC4732205.

Davydov, R., Fleischhacker, A. S., Bagai, I., Hoffman, B. M., and Ragsdale, S. W. (2016) Comparison of the mechanisms of heme hydroxylation by heme oxygenases-1 and -2: kinetic and cryoreduction studies, Biochemistry 55: 62-68. PMC4745887

Gibson, M.I., Chen, P.Y.-T., Johnson, A.C., Pierce, E., Can, M. Ragsdale, S.W., Drennan, C.L. (2016) One-carbon chemistry of oxalate oxidoreductase captured by X-ray crystallography. Proc. Natl. Acad Sci USA 113: 320-325. PMC4720323.

Carter, E. L., Gupta, N., and Ragsdale, S. W. (2015) High Affinity Heme Binding to a Heme Regulatory Motif on the Nuclear Receptor Rev-erbβ Leads to its Degradation and Indirectly Regulates its Interaction with Nuclear Receptor Corepressor J. Biol. Chem. 2912196-2222PMC4732205.

Davydov, R., Fleischhacker, A. S., Bagai, I., Hoffman, B. M., and Ragsdale, S. W. (2015) Comparison of the mechanisms of heme hydroxylation by heme oxygenases-1 and -2: kinetic and cryoreduction studies, Biochemistry, 5562-68.  PMC4745887.

Gibson, M.I., Chen, P.Y.-T., Johnson, A.C., Pierce, E., Can, M. Ragsdale, S.W., Drennan, C.L. (2015) One-carbon chemistry of oxalate oxidoreductase captured by X-ray crystallography. Proc. Natl. Acad Sci USA, 113320-325.  PMC4720323.

Wang, V.C.-C., Islam, S.T.A., Can, M., Ragsdale, S.W. & Armstrong, F.A. (2015) Investigations by Protein Film Electrochemistry of Alternative Reactions of Nickel-Containing Carbon Monoxide Dehydrogenase. The Journal of Physical Chemistry B, 11913690-7.  PMC4663994.

Gibson, M.I., Brignole, E., Pierce, E., Can, M. Ragsdale, S.W., Drennan, C.L. (2015) Structure of an oxalate oxidoreductase provides insight into microbial 2-oxoacid metabolism, Biochemistry 54, 4112-20. PMC4498597

Bagai, I., Sarangi, R., Fleischhacker, A.S., Sharma, A., Hoffman, B.M., Zuiderweg, E., and Ragsdale, S.W. (2015) Spectroscopic studies reveal that the heme regulatory motifs of heme oxygenase-2 are dynamically disordered and exhibit redox-dependent interaction with heme, Biochemistry 54, 2693-708. PMC4423204.

Fleischhacker, A.S., Sharma, A., Choi, M., Spencer, A.M., Bagai, I., Hoffman, B.M., and Ragsdale, S.W. (2015) The C-terminal heme regulatory motifs of heme oxygenase-2 are redox-regulated heme binding sites, Biochemistry 54, 2709-18.

Wongnate, T., and Ragsdale, S. W. (2015) The Reaction Mechanism of Methyl-Coenzyme M Reductase: How an Enzyme Enforces Strict Binding Order, Journal of Biological Chemistry 290, 9332-9334. PMC4392240.

2013-2014

Andreas Bachmeier, A, Hall, S., Ragsdale, S.W., and Armstrong, F.A. (2014) Selective Visible-Light-Driven CO2 Reduction on a p‐Type Dye-Sensitized NiO Photocathode. Journal of the American Chemical Society, 136, 13518-13521.

Spencer, A. M., Bagai, I., Becker, D. F., Zuiderweg, E. R. P., and Ragsdale, S. W. (2014) Protein-protein interactions in the mammalian heme degradation pathway: Heme Oxygenase-2, Cytochrome P450 Reductase and Biliverdin Reductase. Journal of Biological Chemistry 289, 29836-29858.  PMC4207996.

Wang, V.C., Ragsdale, S.W., Armstrong, F.A. (2014) Investigations of the Efficient Electrocatalytic Interconversions of Carbon Dioxide and Carbon Monoxide by Nickel-Containing Carbon Monoxide Dehydrogenases, in The Metal-Driven Biogeochemistry of Gaseous Compounds in the Environment, Eds P.M.H. Kroneck, M.E. Sosa Torres; Vol. 14 of Metal Ions in Life Sciences; Eds A. Sigel, H. Sigel, R.K.O. Sigel; Springer Science + Business Media, Dordrecht, 71-97.  PMC4261625.

Ragsdale, S.W. (2014) Biochemistry of Methyl-Coenzyme M Reductase: The Nickel Metalloenzyme that Catalyzes the Final Step in Synthesis and the First Step in Anaerobic Oxidation of the Greenhouse Gas Methane, in The Metal-Driven Biogeochemistry of Gaseous Compounds in the Environment, Eds P.M.H. Kroneck, M.E. Sosa Torres; Vol. 14 of Metal Ions in Life Sciences; Eds A. Sigel, H. Sigel, R.K.O. Sigel; Springer Science + Business Media, Dordrecht, 2014, Chapter 4, 125-145.

Can, M., Armstrong, F. A., and Ragsdale, S. W. (2014) Structure, Function, and Mechanism of the Nickel Metalloenzymes, CO Dehydrogenase, and Acetyl-CoA Synthase, Chemical Reviews, 114: 4149-4174

Carter, E. L., and Ragsdale, S. W. (2014) Modulation of nuclear receptor function by cellular redox poise, Journal of Inorganic Biochemistry 133: 92-103 . PMC3986263

Bachmeier, A., Wang, V.C., Woolerton, T.W., Bell, S., Fontecilla-Camps, J.C., Can, M., Ragsdale, S.W., Chaudhary, Y.S., and Armstrong, F.A. How light-harvesting semiconductors can alter the bias of reversible electrocatalysts in favor of H2 production and CO2 reduction. Journal of the American Chemical Society (2013) 135: 15026-32 . PMC: 3838662.

Wang VC, Ragsdale SW, Armstrong FA. Investigations of two bidirectional carbon monoxide dehydrogenases from Carboxydothermus hydrogenoformans by protein film electrochemistry. Chembiochem. (2013) 14: 1845-51 . PMC3955222

Zhou, Y., Dorchak, A.E., and Ragsdale, S.W. (2013) In vivo activation of methyl-coenzyme M reductase by carbon monoxide, Frontiers in Microbiology 4, 69 . PMC3612591.

Wang, V.C., Can, M., Pierce, E., Ragsdale, S.W., and Armstrong, F.A. (2013) A unified electrocatalytic description of the action of inhibitors of nickel carbon monoxide dehydrogenase, Journal of the American Chemical Society 135: 2198-2206 . PMC: 3894609.

Appel, A., Bercaw, J., Bocarsly, A., Dobbek, H., DuBois, D., Dupuis, M., Ferry, J., Fujita, E., Hille, R., Kenis, P., Kerfeld, C., Morris, R., Peden, C., Portis, A., Ragsdale, S.W., Rauchfuss, T., Reek, J., Seefeldt, L., Thauer, R., and Waldrop, G. (2013) Frontiers, Opportunities, and Challenges in Biochemical and Chemical Catalysis of CO2 Fixation, Chemical Reviews 113: 6621-6658 . PMC3895110.

2011-2012

Ando, N., Kung, Y., Can, M., Bender, G., Ragsdale, S.W., and Drennan, C. L. (2012) Transient B12-Dependent Methyltransferase Complexes Revealed by Small-Angle X-ray Scattering, Journal of the American Chemical Society 134, 17945-17954 . PMC3484714

Kung, Y., Ando, N., Doukov, T.I., Blasiak, L. C., Bender, G., Seravalli, J., Ragsdale, S.W., and Drennan, C.L. (2012) Visualising molecular juggling within a B12-dependent methyltransferase complex, Nature 484: 265-269.

Chaudhary, Y. S., Woolerton, T. W., Allen, C. S., Warner, J. H., Pierce, E., Ragsdale, S.W., and Armstrong, F. A. (2012) Visible light-driven CO2 reduction by enzyme-coupled CdS nanocrystals, Chemical Communications 48: 58-60.

Bender, G., Pierce, E., Hill, J. A., Darty, J. E., and Ragsdale, S.W. (2012) Metal Centers in the Anaerobic Microbial Metabolism of CO and CO2, Metallomics 3: 797-815.

Reed, G.H., Ragsdale, S.W., and Mansoorabadi, S.O. (2012) Radical reactions of thiamin pyrophosphate in 2-oxoacid oxidoreductases, Biochimica Biophysica Acta 1824: 1291-1298.

Ragsdale, S.W., Yi, L., Bender, G., Gupta, N., Kung, Y., Yan, L., Stich, T.A., Doukov, T., Leichert, L., Jenkins, P.M., Bianchetti, C.M., George, S.J., Cramer, S.P., Britt, R.D., Jakob, U., Martens, J.R., Phillips, G.N., and Drennan, C.L. (2012) Redox, haem and CO in enzymatic catalysis and regulation, Biochem Soc Trans 40: 501-507.

Ragsdale, S.W., Gupta, N., Bagai, I., Spencer, A. M., and Carter, E. (2012) Thiol/Disulfide Redox Switches as a Regulatory Mechanism in Heme-binding Proteins, In Porphyrin Biochemistry. Handbook of Applications to Biomedicine and Bio-inspired Energy (Ferriera, G., Ed.), p in press, World Scientific Publishers.

Ragsdale, S.W., Pierce, E., and Bender, G. (2012) CO Dehydrogenase/Acetyl-CoA Synthase, In Encyclopedia of Metalloproteins (Uversky, V., Kretsinger, R.H., and Permyakov, E.A., Eds.), Springer, in press.

Zhou, Y., Sliwa, D.A., and Ragsdale, S.W. (2012) Biochemistry of Methyl-CoM Reductase and Coenzyme F430, In Handbook of Porphyrin Science (Kadish, K. M., Smith, K. M., and Guilard, R., Eds.), World Scientific Publishing, in press. 

Methods Enzymol (Rosenzweig, A. C., and Ragsdale, S.W., Eds.) 2011, Volumes 494 and 495 Methods in Methane Metabolism. Vol 494 is on Methanogenesis and Vol 495 is on Methanotrophy. Academic Press, San Diego. Click here for Methanogenesis and here for Methanotrophy.

Rosenzweig AC, Ragsdale, SW (2011) Preface, Methods Enzymol 495, xv-xvi.

Bagai, I., Ragsdale, S.W., and Zuiderweg, E. R. (2011) Pseudo-4D triple resonance experiments to resolve HN overlap in the backbone assignment of unfolded proteins, Journal of Biomolecular NMR 49: 69-74.

Ragsdale, S.W. (2011) How two amino acids become one. Nature 471: 583-584.

Ragsdale, S.W. and Yi, L. (2011) Thiol/Disulfide Redox Switches as Regulators of Heme-Dependent Processes, Antioxidants & Redox Signaling. 14: 1039-1047. PMC3042308

Woolerton, T.W., Sheard, S., Pierce, E., Ragsdale, S.W., and Armstrong, F.A. (2011) CO2 photoreduction at enzyme-modified metal oxide nanoparticles. Energy & Environmental Science 4: 2393-2399.

Cedervall, P.E., Dey, M., Li, X., Sarangi, R, Hedman, Ragsdale, S.W., and Wilmot, C.M. (2011) Structural analysis of a Ni-methyl species in methyl-coenzyme M reductase from Methanothemobacter marburgensis, Journal of the American Chemical Society, 133: 5626-5628.

Gupta, N. & Ragsdale, S.W. (2011) Thiol-disulfide redox dependence of heme binding and heme ligand switching in a nuclear hormone receptor Rev-erb-Beta, Journal of Biological Chemistry 286: 4392-4403.

2009-2010

Bender, G. & Ragsdale, S.W. (2010) Evidence that Ferredoxin Interfaces with an Internal Redox Shuttle in Acetyl-CoA Synthase During Reductive Activation and Catalysis, Biochemistry 50: 276-286.

Bagai, I., Ragsdale, S.W. & Zuiderweg, E.R.P. (2010) Pseudo-4D triple resonance experiments to resolve HN overlap in the backbone assignment of unfolded proteins, Journal of Biomolecular NMR, 49: 69-74.

Dey, M., Xi, X., Kunz, R.C., and Ragsdale, S.W. (2010) Detection of Organometallic and Radical Intermediates in the Catalytic Mechanism of Methyl-Coenzyme M Reductase Using the Natural Substrate Methyl-Coenzyme M and a Coenzyme B Substrate Analog, Biochemistry 49: 10902-10911.

Pierce, E., Becker, D.F., and Ragsdale, S.W. (2010) Identification and Characterization of Oxalate Oxidoreductase, a Novel Thiamine Pyrophosphate-dependent 2-Oxoacid Oxidoreductase that Enables Anaerobic Growth on Oxalate, Journal of Biological Chemistry 285: 40515-40524.

Bender, G., Stich, T. A., Yan, L., Britt, R. D., Cramer, S. P., and Ragsdale, S.W. (2010) Infrared and EPR Spectroscopic Characterization of a Ni(I) Species Formed by Photolysis of a Catalytically Competent Ni(I)-CO Intermediate in the Acetyl-CoA Synthase Reaction, Biochemistry 49: 7516-7523. Fac 1000 Pick.

Cedervall, P. E., Dey, M., Pearson, A. R., Ragsdale, S.W., and Wilmot, C. M. (2010) Structural Insight into Methyl-Coenzyme M Reductase Chemistry using Coenzyme B Analogues, Biochemistry 49: 7683-7693.PMID: 20707311

Li, X., Telser, J., Hoffman, B. M., Gerfen, G., and Ragsdale, S.W. (2010) Observation of organometallic and radical intermediates formed during the reaction of methyl-coenzyme M reductase with bromoethanesulfonate, Biochemistry 49: 6866-6876. Fac 1000 Pick.

Yi, L., Morgan, J. T., and Ragsdale, S.W. (2010) Identification of a thiol/disulfide redox switch in the human BK channel that controls its affinity for heme and CO, Journal of Biological Chemistry 285: 20117-201273.

Gardner, J. D., Yi, L.,Ragsdale, S.W., and Brunold, T. C. (2010) Spectroscopic Insights into Axial Ligation and Active-site H-bonding in Substrate-Bound Human Heme Oxygenase-2, Journal of Biological Inorganic Chemistry, 1117-1127 . PMID: 20502928

Woolerton, T. W., Sheard, S., Reisner, E., Pierce, E., Ragsdale, S.W., and Armstrong, F. A. (2010) Efficient and clean photo-reduction of CO2 to CO by enzyme-modified TiO2 nanoparticles using visible light, Journal of the American Chemical Society 132: 2132-2133.

Ragsdale, S.W. and Seravalli, J. (2010) Expanding the Biological Periodic Table, Chemistry & Biology, 17: 793-794.

Dey, M., Li, X., Zhou, Y., and Ragsdale, S.W. (2010) Evidence for Organometallic Intermediates in Bacterial Methane Formation Involving the Nickel Coenzyme F430, In Metal Ions in Life Sciences, Vol. 7. Sigel, A. & H. Sigel, Eds. Royal Society of Chemistry. Cambridge, UK., 71-110.

Ragsdale, S.W. (2009) Nickel-based enzymatic systems. Journal of Biological Chemistry 284: 18571-18575.

Welte, C., Kallnik, V., Grapp, M., Bender, G., Ragsdale, S., and Deppenmeier, U. (2009) Function of Ech hydrogenase in ferredoxin-dependent membrane-bound electron transport in Methanosarcina mazei, Journal of Bacteriology 192:. 674-678.

Lazarus, O., Woolerton, T., Parkin, A., Lukey, M., Reisner, E., Seravalli, J., Pierce, E., Ragsdale, S.W., Sargent, F. & Armstrong, F. (2009) Water-Gas Shift Reaction Catalyzed by Redox Enzymes on Conducting Graphite Platelets, Journal of the American Chemical Society 131:. 14154-14155.

Kung, Y., Doukov, T.I., Seravalli, J., Ragsdale, S.W., Drennan, C.L. (2009) Crystallographic snapshots of cyanide- and water-bound C-clusters from bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase, Biochemistry 48: 7432-7440.

Yi, L., Jenkins, P. M., Leichert, L. I., Jakob, U., Martens, J. R., and Ragsdale, S.W. (2009) The heme regulatory motifs in heme oxygenase-2 form a thiol/disulfide redox switch that responds to the cellular redox state, Journal of Biological Chemistry 284: 20556-20561.

Sarangi, R., Dey, M., and Ragsdale, S.W. (2009) Geometric and Electronic Structures of the Ni(I) and Methyl-Ni(III) Intermediates of Methyl-Coenzyme M Reductase, Biochemistry 48: 3146-3156.

2007-2008

Gupta, N. and Ragsdale, S.W. (2008) Dual roles of an essential cysteine residue in activity of a redox-regulated bacterial transcriptional activator, Journal of Biological Chemistry 283: 28721-28728.

Pierce, E., Xie, G., Barabote, R. D., Saunders, E., Han, C. S., Detter, J. C., Richardson, P., Brettin, T. S., Das, A., Ljungdahl, L. G., and Ragsdale, S.W. (2008) The Complete Genome Sequence of Moorella thermoacetica, Environmental Microbiology 10: 2550-2573.

Seravalli, J. and Ragsdale, S.W. (2008) 13C-NMR characterization of an exchange reaction between CO and CO2 catalyzed by carbon monoxide dehydrogenase, Biochemistry 47: 6770-6781. Faculty of 1000 Pick

Seravalli, J and Ragsdale, S.W. (2008) Pulse-chase studies of the synthesis of acetyl-coenzyme A by carbon monoxide dehydrogenase/acetyl-CoA synthase: Evidence for a random mechanism of methyl and CO addition, Journal of Biological Chemistry 283: 8384-8394.

Doukov, T.I., Blasiak, L.C., Seravalli, J., Ragsdale, S.W., and Drennan, C.L. (2008) Xenon in and at the end of the tunnel of bifunctional Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase Biochemistry 47: 3474-3483.

Kunz, R. C., Dey, M., and Ragsdale, S.W. (2008) Characterization of the Thioether Product Formed From the Thiolytic Cleavage of the Alkyl-Nickel Bond in Methyl-Coenzyme M Reductase Biochemistry 47: 2661-2667.

Ragsdale, S.W., and Pierce, E. (2008) Acetogenesis and the Wood-Ljungdahl Pathway of CO2 Fixation, Biochim Biophys Acta - Proteins and Proteomics 10:18801467.

Ragsdale, S.W. (2008) Catalysis of Methyl Group Transfers Involving Tetrahydrofolate and B12, in: G. Litwack (Ed.), Vitamins and Hormones, vol. 79, Folic Acid and Folates, Elsevier, Inc., Amsterdam, The Netherlands, pp 293-324.18804699.

Ragsdale, S.W. (2008) Enzymology of the Wood-Ljungdahl Pathway of Acetogenesis, Annals of the N. Y. Academy of Sciences, 1125: 129-136.18378591.

Ragsdale, S.W. (2008) Heme oxygenase, in R. Banerjee (ed.), Redox Biochemistry, Wiley and Sons, Hoboken, NJ, Chpt. 3.7, pp. 131-134.

Ragsdale, S.W. (2008) Redox enzymology, in R. Banerjee (ed.), Redox Biochemistry, Wiley and Sons, Hoboken, NJ, Chpt 4.6, pp. 173-177.

Seravalli, J., and Ragsdale, S.W. (2008) Electron Paramagnetic Resonance in R. Banerjee (ed.), Redox Biochemistry, Wiley and Sons, Hoboken, NJ, Chpt 6.2, pp. 237-247.

Ragsdale, S.W. (2007) Nickel and the Carbon Cycle. Journal of Inorganic Biochemistry 101: 165766.

Bianchetti C. M., Li, Y., Ragsdale, S.W., and Phillips, G.N., Jr. (2007) Comparison of Apo and Heme-bound Crystal Structures of a Truncated Human Heme Oxygenase-2, Journal of Biological Chemistry 282: 37624-37631.

Dey M, Telser, J, Kunz R.C., Lees, N.S., Ragsdale, S.W., Hoffman, B. (2007) Biochemical and spectroscopic studies of the electronic structure and reactivity of a methyl-Ni species formed on Methyl-Coenzyme M Reductase, Journal of the American Chemical Society 129: 11030-2. Faculty of 1000 Pick

Yi, Li and Ragsdale, S.W. (2007) Evidence that the heme regulatory motifs in heme oxygenase-2 serve as a thiol/disulfide redox switch regulating heme binding. Journal of Biological Chemistry, 282: 21056-21067.

Doukov, T.I., Hemmi, H., Drennan, C.L., and Ragsdale, S.W. (2007) Structural And Kinetic Evidence For An Extended Hydrogen Bonding Network In Catalysis Of Methyl Group Transfer: Role Of An Active Site Asparagine Residue In Activation Of Methyl Transfer By Methyltransferases, Journal of Biological Chemistry 282: 6609-6618. Paper of the week, Faculty of 1000 Pick.

Selected 1999-2006

Kunz, R., Horng, Y.C., and Ragsdale, S.W. (2006) Interaction and reaction of methyl-coenzyme M reductase with its potent inhibitor, 3-bromopropane sulfonate. Journal of Biological Chemistry 281: 34663-34676.

Dey, M., Kunz, R., Heuvelen, K. M. V., Craft, J. L., Horng, Y.-C., Tang, Q., Bocian, D. F., George, S. J., Brunold, T. C., Ragsdale, S.W. (2006) Cofactor- versus Metal-Centered Reduction of the Coenzyme F430. Biochemistry 45:11915-11933.

Pop, S.M., Gupta, N., Raza, A.S., and Ragsdale, S.W. (2006) Transcriptional activation of dehalorespiration: identification of redox-active cysteines regulating dimerization and substrate binding. Journal of Biological Chemistry 281: 26382-90.

Joyce, M. G., Levy, C., Gabor, K., Pop, S. M., Biehl, B. D., Doukov, T. I., Ryter, J. M., Mazon, H., Smidt, H., van den Heuvel, R. H. H., Ragsdale, S.W., van der Oost, J., and Leys, D. (2006) CprK crystal structures reveal mechanism for transcriptional control of halorespiration. Journal of Biological Chemistry: 281: 28318-25.

Mansoorabadi, SO., Seravalli, J., Furdui, C., Krymov, V., Gerfen, GJ., Begley, TP., Melnick, J., Ragsdale, SW, and Reed, GH. (2006) EPR Spectroscopic and Computational Characterization of the Hydroxyethylidine-Thiamin Pyrophosphate Radical Intermediate of Pyruvate:Ferredoxin Oxidoreductase. Biochemistry 45: 7122-7131.

Astashkin, A.V., Seravalli, J., Mansoorabadi, S.O., Reed, G.H., and Ragsdale, S.W. (2006) Pulsed Electron Paramagnetic Resonance Experiments Identify the Radical Intermediates in the Pyruvate Ferredoxin Oxidoreductase Catalytic Cycle. Journal of the American Chemical Society 128: 3888-9.

Stich, T.A., Seravalli, J., Venkateshrao, S., Spiro, T.G., Ragsdale, S.W. and Brunold, T.C. (2006) Spectroscopic Studies of the Corrinoid/Iron-Sulfur Protein from Moorella thermoacetica, Journal of the American Chemical Society 128: 5010-5020.

Frantom, P.A., Seravalli,J., Ragsdale, S.W., and Fitzpatrick, P.F. (2006) Reduction and oxidation of the active site iron in tyrosine hydroxylase: kinetics and specificity, Biochemistry 45: 2372-9.
Ragsdale, S.W. (2006) Metals and their scaffolds in catalyzing difficult reactions. Chemical Reviews, 106: 3317-37.

Ragsdale, S.W. (2006) One-carbon chemistry: CO2, CO, CH4, formate: 1. Reductive chemistry. In, I. Bertini, H. Gray, E.I. Stiefel, J. S. Valentine (ed.), Biological Inorganic Chemistry: Structure and Reactivity. University Science Books. Chpt 12, pp. 452-467.

George, S. J., Seravalli, J., and Ragsdale, S.W. (2005) EPR and infrared spectroscopic evidence that a kinetically competent paramagnetic intermediate is formed when acetyl-coenzyme A synthase reacts with CO. Journal of the American Chemical Society 127:13500-1.

Pop, S., Kolarik, R.J., and Ragsdale, S.W. (2004) Regulation of anaerobic dehalorespiration by the transcriptional activator CprK. Journal of Biological Chemistry 279: 49910-49918.

Dumitru, R. V., and Ragsdale, S.W. (2004) Mechanism of b-RFA-P Synthase, a Key Enzyme in the Methanopterin Biosynthetic Pathway. Journal of Biological Chemistry 279: 39389-39395.

Craft, J. L., Y.-C. Horng, Ragsdale, S.W., and T. C. Brunold (2004) Nickel Oxidation States of F430 Cofactor in Methyl-Coenzyme M Reductase. Journal of the American Chemical Society 126: 4068 - 4069

Gu, W., J. Seravalli, Ragsdale, S.W., and S. P. Cramer (2004) CO-Induced Structural Rearrangement of the C-cluster in Carboxydothermus hydrogenoformans CO Dehydrogenase - Evidence from Ni K-Edge X-ray Absorption Spectroscopy. Biochemistry 43: 9029-9035.

Seravalli, J., Xiao, Y., Gu, W., Cramer, S.P., Antholine, W.E., Krymov, V., Gerfen, G.J., and Ragsdale, S.W. (2004) Evidence That Ni-Ni Acetyl-CoA Synthase Is Active And That The Cu-Ni Enzyme Is Not. Biochemistry 43: 3944 - 3955.

Craft, J.L., Horng, Y.-C., Ragsdale, S.W., and Brunold, T.C. (2004) Spectroscopic and computational studies of the nickel-containing F430 cofactor in methyl-coenzyme M reductase. Journal of Biological Inorganic Chemistry 9: 77-89.

Chen, J., Huang, S., Seravalli, J., Jr., H.G., Swartz, D.J., Ragsdale, S.W., and Bagley, K.A. (2003) Infrared studies of carbon monoxide binding to carbon monoxide dehydrogenase/acetyl-CoA synthase from Moorella thermoacetica. Biochemistry 42:14822-14830.

Dumitru, R., Palencia, H., Schroeder, S.D., DeMontigny, B.A., Takacs, J.M., Rasche, M.E., Minor, J.L., and Ragsdale, S.W. (2003) Targeting methanopterin biosynthesis to inhibit methanogenesis. Applied and Environmental Microbiology 69: 7236-7241.

Singh, K., Horng, Y.-C., and Ragsdale, S.W. (2003) Rapid ligand exchange in the MCRred1 form of methyl-coenzyme M reductase. Journal of the American Chemical Society 125: 2436-2443.
Seravalli, J., Gu, W., Tam, A., Strauss, E., Begley, T.P., Cramer, S.P., and Ragsdale, S.W. (2003) Functional copper at the acetyl-CoA synthase active site. Proceedings of the National Academy Of Science USA: 100: 3689-3694.

Doukov, T. I., Iverson, T., Seravalli, J., Ragsdale, S.W., and Drennan. C. L. (2002) An Unique Ni-Fe-Cu Center in the Crystal Structure of Bifunctional Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase. Science 298: 567-572.

Tang, Q., Carrington, P. E., Horng, Y.-C., Maroney, M. J., Ragsdale, S.W., and Bocian. D. F. (2002) X-Ray Absorption and Resonance Raman Studies of Methyl-Coenzyme M Reductase Indicating That Ligand Exchange and Macrocycle Reduction Accompany Reductive Activation. Journal of the American Chemical Society 124: 13242-13256.

Furdui, C., and Ragsdale, S.W. (2002) The Roles of Coenzyme A in the Pyruvate:Ferredoxin Oxidoreductase Reaction Mechanism: Rate Enhancement of Electron Transfer from a Radical Intermediate to an Iron-Sulfur Cluster, Biochemistry, 41: 9921-9937.

Seravalli, J., Kumar, M., and Ragsdale, S.W. (2002) Rapid Kinetic Studies of Acetyl-CoA Synthesis: Evidence Supporting the Catalytic Intermediacy of a Paramagnetic NiFeC Species in the Autotrophic Wood-Ljungdahl Pathway. Biochemistry 41: 1807-1819.

Boll, M., Fuchs, G., Meier, C., Trautwein, A., Kasmi, A.E., Ragsdale, S.W., Buchanan, G., and Lowe, D.J. (2001) Redox centers of 4-hydroxybenzoyl-CoA reductase, a member of the xanthine oxidase family of molybdenum containing enzymes. Journal of Biological Chemistry 276: 47853-62.

Seravalli, J., Brown, K.L., and Ragsdale, S.W. (2001) Acetyl-Coenzyme A Synthesis From Unnatural Methylated Corrinoids: Requirement for “Base-Off” Coordination at Cobalt, Journal of the American Chemical Society 123: 1786-1787.

Murakami, E., Deppenmeier, U., and Ragsdale, S.W. (2001) Characterization of the Intramolecular Electron Transfer Pathway from 2-Hydroxyphenazine to the Heterodisulfide Reductase from Methanosarcina thermophila. Journal of Biological Chemistry 276: 2432-2439.

Naidu, D., and Ragsdale, S.W. (2001) Characterization of a three-component vanillate O-demethylase from Moorella thermoacetica. Journal of Bacteriology 183: 3276-81.

Telser, J., Davydov, R., Horng, Y.C., Ragsdale, S.W., and Hoffman, B.M. (2001) Cryoreduction of methyl-coenzyme M reductase: EPR characterization of forms, MCR(ox1) and MCR(red1). Journal of the American Chemical Society

Horng, Y.-C., Becker, D.F., and Ragsdale, S.W. (2001) Requirement of Coenzyme B for Cleavage of the C-S bond of methyl-SCoM. Biochemistry 40:12875-12885.

Krasotkina, J., Walters, T., Maruya, K.A., and Ragsdale, S.W. (2001) Characterization of the B12- and Iron-Sulfur Containing Reductive Dehalogenase from Desulfitobacterium chlororespirans. Journal of Biological Chemistry 276: 40991-7.

Seravalli, J., and Ragsdale, S.W. (2000) Channeling of Carbon Monoxide During Anaerobic Carbon Dioxide Fixation Biochemistry 39: 1274-1277.

Telser, J., Horng, Y.-C., Becker, D., Hoffman, B., and Ragsdale, S.W. (2000) On the assignment of nickel oxidation states of the Ox1 and Ox2 Forms of Methyl-Coenzyme M Reductase. Journal of the American Chemical Society 122: 182-183.

Murakami, E., and Ragsdale, S.W. (2000) Evidence for Intersubunit Communication During Acetyl-CoA Cleavage by the Multienzyme CO Dehydrogenase/Acetyl-CoA Synthase Complex from Methanosarcina thermophila: Evidence that the Beta Subunit Catalyzes C-C and C-S Bond Cleavage. Journal of Biological Chemistry 275: 4699-4707.

Doukov, T., Ragsdale, S.W., and Stezowski, J. (2000) Crystal structure of a methyltetrahydrofolate and corrinoid dependent methyltransferase, Structure with Folding and Design, 8: 817-830.

Furdui, C., and Ragsdale, S.W. (2000) The role of pyruvate: ferredoxin oxidoreductase in pyruvate synthesis during autotrophic growth by the Wood-Ljungdahl pathway. Journal of Biological Chemistry 275: 28494-28499.

Ralston, C.Y., Wang, H., Ragsdale, S.W., Dumar, M., Spangler, N.J., Ludden, P.W., Gu, W., Jones, R.M., Patil, D.S., and Cramer, S.P. (2000) Characterization of heterogeneous nickel sites in CO dehydrogenases from Clostridium thermoaceticum and Rhodospirillum rubrum by nickel L-edge X-ray spectroscopy. Journal of the American Chemical Society 122: 10553-10560.

Arendsen, S., Soliman, M., and Ragsdale, S.W. (1999) Nitrate-Dependent Regulation Of Acetate Biosynthesis And Nitrate Respiration by Clostridium thermoaceticum. Journal of Bacteriology 181: 1489-1495.

Bouchev, V.F., Furdui, C.M., Menon, S., Muthukumaran, R.B., Ragsdale, S.W., and McCracken, J. (1999) ENDOR studies of pyruvate: ferredoxin oxidoreductase reaction intermediates. Journal of the American Chemical Society 121: 3724-3729.

Seravalli, J., Zhao, S.Y., and Ragsdale, S.W. (1999) Mechanism of Transfer of the Methyl Group from (6S)-Methyltetrahydrofolate to the Corrinoid/Iron-Sulfur Protein Catalyzed by the Methyltransferase from Clostridium thermoaceticum: A Key Step in the Wood-Ljungdahl Pathway of Acetyl-CoA Synthesis. Biochemistry 38: 5728-5735.

Seravalli, J., Shoemaker, R.K., Sudbeck, M.J., and Ragsdale, S.W. (1999) Binding of (6R,S)-Methyltetrahydrofolate to Methyltransferase from Clostridium thermoaceticum: Role of Protonation of Methyltetrahydrofolate in the Mechanism of Methyl Transfer. Biochemistry 38: 5736-5745.

Menon, S., and Ragsdale, S.W. (1999) The role of an iron-sulfur cluster in an enzymatic methylation reaction: methylation of CO dehydrogenase/acetyl-CoA synthase by the methylated corrinoid iron-sulfur protein. Journal of Biological Chemistry 274: 11513-8.

Older Invited Review Articles

Drennan, C. L., Doukov, T. I., and Ragsdale, S.W. (2004) The Metalloclusters of Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase: A Story in Pictures. J. Biol Inorg Chem: 9:511-515.

Ragsdale, S.W. (2004) Life with carbon monoxide. CRC Crit Rev Biochem and Mol Biol., 39:165-195.

Banerjee, R. and Ragsdale, S.W. (2003) B12 Biochemistry. Annual Review of Biochemistry, 72: 209-247.

Ragsdale, S.W. (2003) Pyruvate Ferredoxin Oxidoreductase. Chemical Reviews, 103: 2333-2346.

Ragsdale, S.W. (2003) Biochemistry of Methylcoenzyme M Reductase and Coenzyme F430. In K. M. Kadish, R. Guilard, and K. Smith (ed.), Porphyrin Handbook, Bioinorganic and Bioorganic Chemistry. Academic Press, New York. Vol. 11: 205-228.

Ragsdale, S.W. (2003) Anaerobic one-carbon catalysis, p. 665-695. In Horvath, I.T., Iglesia, E., Klein, M.T., Lercher, J.A., Russell, A.J., and Stiefel, E.I. (ed.), Encyclopedia of Catalysis, vol. 1. John Wiley and Sons, Inc., New York.

Ragsdale, S.W. (2000) Ni containing CO dehydrogenase and hydrogenase, p. 487-518. In A. Holzenburg and N. Scrutton (ed.), Enzyme-catalyzed electron and radical transfer, vol. 35. Plenum Press, New York.

Fonticilla-Camps, J.-C., and Ragsdale, S.W. (1999) Nickel-iron-sulfur active sites: hydrogenase and CO dehydrogenase, In R. Cammack and A. G. Sykes (ed.), Advances in Inorganic Chemistry vol 47, 283-333. Academic Press, Inc., San Diego.

Ragsdale, S.W. (1999) The Acetogenic Corrinoid Proteins, p. 633-654. In R. Banerjee (ed.), Vitamin B12, vol. 1. John Wiley and Sons, New York.

 
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