Stephen Ragsdale, Ph.D.

David Ballou Collegiate Professor, Biological Chemistry

Office: 5220D MSRB III
Lab: 5200 MSRB III
1150 W. Medical Center Drive
Ann Arbor, MI 48109-5606


(734) 615-4621

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 (Rev-Erb). 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, Rev-Erb 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.

The Ragsdale laboratory has been certified as a Platinum Level Sustainable Laboratory by the Office of Campus Sustainability at the University of Michigan.

The Ragsdale laboratory is committed to diversity, equity and inclusion. All are welcome, regardless of race, ethnicity, color, gender, sexual orientation, gender identity and expression, country of origin, religion, or disability status.


Positions for Ph.D. students and postdoctoral scholars are available for all Ragsdale Lab projects. Postdoctoral candidates with demonstrated research productivity and expertise in biochemistry, cell biology, metallobiochemistry, and enzymology are especially encouraged to apply. Please send the following to Stephen Ragsdale: a cover letter that describes your past research experience and motivation for applying to the Ragsdale Lab, a brief description of proposed research for your postdoctoral project, your most relevant published papers (for multi-author papers, please describe your contribution), and names and contact information for 3 or more potential references (letters are not needed during the initial stage).

Ph.D. candidates should apply to one of the following programs at the University of Michigan: Program in Biomedical Sciences (Biological Chemistry or Cellular and Molecular Biology), Program in Chemical Biology. All programs allow graduate students to rotate through multiple labs in the first year, providing a diversity of research experiences prior to selecting a lab.

Program Affiliations

Cellular and Molecular Biology Program
Chemical Biology Interface Training Program
Program in Chemical Biology
University of Michigan Energy Institute

Funding & Collaborations

Ragsdale Lab Funding
Ragsdale Lab Collaborators

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

Enzyme Purification Blues music video on ASBMB Today's YouTube channel

Honors & Awards

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

Editorial Boards

Journal of Inorganic Biochemistry, 2021–present
Journal of Biological Chemistry, 2012–present
Frontiers in Microbiological Chemistry, 2011–present
BBA Proteins and Proteomics, 2007–2012
Current Opinions in Chemical Biology, 2006–present
Archives of Microbiology, 2003–2006
Archives of Biochemistry and Biophysics, 1999–2002
Journal of Biological Chemistry, 1997–2008
Journal of Bacteriology, 1996–2004
Biofactors, 1987–2016


Published Articles or Reviews


Characterization of the Methyl- and Acetyl-Ni Intermediates in Acetyl-CoA Synthase Formed During Anaerobic CO2 and CO Fixation.
Can M, Abernathy M, Wiley S, Griffith C, James C, Xiong J, Guo Y, Hoffman B, Ragsdale SW, Sarangi R.
J. Am. Chem. Soc. 2023; 145: 13696–708. Read news article


Heme delivery to heme oxygenase-2 involves glyceraldehyde-3-phosphate dehydrogenase.
Dai Y, Fleischhacker AS, Liu L, Fayad S, Gunawan AL, Stuehr DJ, Ragsdale SW.
Biol Chem. 2022; 403: 1043–53.

Efficient, Light-Driven Reduction of CO2 to CO by a Carbon Monoxide Dehydrogenase-CdSe/CdS Nanorod Photosystem.
White DW, Esckilsen D, Lee SK, Ragsdale SW, Dyer RB.
J Phys Chem Lett. 2022; 13: 5553–6.

XFEL serial crystallography reveals the room temperature structure of methyl-coenzyme M reductase.
Ohmer CJ, Dasgupta M, Patwardhan A, Bogacz I, Kaminsky C, Doyle MD, Chen PY, Keable SM, Makita H, Simon PS, Massad R, Fransson T, Chatterjee R, Bhowmick A, Paley DW, Moriarty NW, Brewster AS, Gee LB, Alonso-Mori R, Moss F, Fuller FD, Batyuk A, Sauter NK, Bergmann U, Drennan CL, Yachandra VK, Yano J, Kern JF, Ragsdale SW.
J Inorg Biochem. 2022; 230: 111768.

Heme oxygenase-2 (HO-2) binds and buffers labile ferric heme in human embryonic kidney cells.
Hanna DA, Moore CM, Liu L, Yuan X, Dominic IM, Fleischhacker AS, Hamza I, Ragsdale SW, Reddi AR.
J Biol Chem. 2022; 298: 101549.

Not a 'they' but a 'we': the microbiome helps promote our well-being.
Ragsdale SW.
J Biol Chem. 2022; 298: 101511.

Regulation of Protein Function and Degradation by Heme, Heme Responsive Motifs, and CO.
Fleischhacker AS, Sarkar A, Liu L, Ragsdale SW.
Crit Rev Biochem Mol Biol. 2022; 57: 16–47.

Biological Carbon Fixation by an Organometallic Pathway: Evidence Supporting the Paramagnetic Mechanism of the Nickel-Iron-Sulfur Acetyl-CoA Synthase.
Ragsdale SW.
In Comprehensive Coordination Chemistry III (Elsevier). 2021; 8.24: 611–33.

Nickel-Sulfonate Mode of Substrate Binding for Forward and Reverse Reactions of Methyl-SCoM Reductase Suggest a Radical Mechanism Involving Long Range Electron Transfer.
Patwardhan A, Sarangi R, Ginovska B, Raugei S, Ragsdale SW.
J. Am. Chem. Soc. 2021; 143: 5481–96.

Ferric heme as a CO/NO sensor in the nuclear receptor Rev-Erbß by coupling gas binding to electron transfer.
Sarkar A, Carter EL, Harland JB, Speelman AL, Lehnert N, Ragsdale SW.
Proc Natl Acad Sci U S A. 2021; 118: e2016717118.

Negative-Stain Electron Microscopy Reveals Dramatic Structural Rearrangements in Ni-Fe-S-Dependent Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase.
Cohen SE, Brignole EJ, Wittenborn EC, Can M, Thompson S, Ragsdale SW, Drennan CL.
Structure. 2021; 29: 43–9.


Heme oxygenase-2 is post-translationally regulated by heme occupancy in the catalytic site.
Liu L, Dumbrepatil AB, Fleischhacker AS, Marsh ENG, Ragsdale SW.
J Biol Chem. 2020; 295: 17227–40.

Crystallographic Characterization of the Carbonylated A-Cluster in Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase.
Cohen SE, Can M, Wittenborn EC, Hendrickson RA, Ragsdale SW, Drennan CL.
ACS Catal. 2020; 10: 9741–6.

13C Electron Nuclear Double Resonance Spectroscopy Shows Acetyl-CoA Synthase Binds Two Substrate CO in Multiple Binding Modes and Reveals the Importance of a CO-Binding "Alcove".
James CD, Wiley S, Ragsdale SW, Hoffman BM.
J Am Chem Soc. 2020; 142: 15362–70.

Structure determination of the HgcAB complex using metagenome sequence data: insights into microbial mercury methylation.
Cooper CJ, Zheng K, Rush KW, Johs A, Sanders BC, Pavlopoulos GA, Kyrpides NC, Podar M, Ovchinnikov S, Ragsdale SW, Parks JM.
Commun Biol. 2020; 3: 320.

The heme regulatory motifs of heme oxygenase-2 contribute to the transfer of heme to the catalytic site for degradation.
Fleischhacker AS, Gunawan AL, Kochert BA, Liu L, Wales TE, Borowy MC, Engen JR, Ragsdale SW.
J Biol Chem. 2020; 295: 5177–91.

Oxygen and Conformation Dependent Protein Oxidation and Aggregation by Porphyrins in Hepatocytes and Light-Exposed Cells.
Maitra D, Carter EL, Richardson R, Rittié L, Basrur V, Zhang H, Nesvizhskii AI, Osawa Y, Wolf MW, Ragsdale SW, Lehnert N, Herrmann H, Omary MB.
Cell Mol Gastroenterol Hepatol. 2019; 8: 659–82.

Kinetics of enzymatic mercury methylation at nanomolar concentrations catalyzed by HgcAB.
Date SS, Parks JM, Rush KW, Wall JD, Ragsdale SW, Johs A.
Appl Environ Microbiol. 2019; 85: e00438–19.

Dynamic and structural differences between heme oxygenase-1 and -2 are due to differences in the C-terminal regions.
Kochert, BA, Fleischhacker, AS, Wales, TE, Becker, DF, Engen, JR, Ragsdale, SW.
J Biol Chem. 2019; 294: 8259–72.

Elusive microbe that consumes ethane found under the sea.
Ragsdale, SW.
Nature. 2019; 568: 40–1.


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 FA.
ACS Catal. 2018; 8: 2789–95.

Stealth reactions driving carbon fixation.
Ragsdale SW.
Science. 2018; 359: 517–8.

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.


Deep-sea secrets of butane metabolism.
Ragsdale SW.
Nature. 2016; 539: 367–8.

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.
Pearl NM, Wilcoxen J, Im S, Kunz R, Darty J, Britt RD, Ragsdale SW, Waskell L.
Biochemistry. 2016; 55: 6558–67

Exploring Hydrogenotrophic Methanogenesis: a Genome Scale Metabolic Reconstruction of Methanococcus maripaludis.
Richards MA, Lie TJ, Zhang J, Ragsdale SW, Leigh JA, Price ND.
J Bacteriol. 2016; 198: 3379–3390.

The radical mechanism of biological methane synthesis by methyl-coenzyme M reductase.
Wongnate T, Sliwa D, Ginovska B, Smith D, Wolf MW, Lehnert N, Raugei S, Ragsdale SW.
Science. 2016; 352: 953–8.

Targeting methanogenesis with a nitrooxypropanol bullet.
Ragsdale SW.
Proc Natl Acad Sci U S A. 2016; 113: 6100–1.

One-carbon chemistry of oxalate oxidoreductase captured by X-ray crystallography.
Gibson MI, Chen PY, Johnson AC, Pierce E, Can M, Ragsdale SW, Drennan CL.
Proc Natl Acad Sci U S A. 2016; 113: 320–5.

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.
Carter EL, Gupta N, Ragsdale SW.
J Biol Chem. 2016; 291: 2196–222.

Comparison of the Mechanisms of Heme Hydroxylation by Heme Oxygenases-1 and -2: Kinetic and Cryoreduction Studies.
Davydov R, Fleischhacker AS, Bagai I, Hoffman BM, Ragsdale SW.
Biochemistry. 2016; 55: 62–8.

Investigations by Protein Film Electrochemistry of Alternative Reactions of Nickel-Containing Carbon Monoxide Dehydrogenase.
Wang VC, Islam ST, Can M, Ragsdale SW, Armstrong FA.
J Phys Chem B. 2015; 119: 13690–7.

The Structure of an Oxalate Oxidoreductase Provides Insight into Microbial 2-Oxoacid Metabolism.
Gibson MI, Brignole EJ, Pierce E, Can M, Ragsdale SW, Drennan CL.
Biochemistry. 2015; 54: 4112–20.

The C-terminal heme regulatory motifs of heme oxygenase-2 are redox-regulated heme binding sites.
Fleischhacker AS, Sharma A, Choi M, Spencer AM, Bagai I, Hoffman BM, Ragsdale SW.
Biochemistry. 2015; 54: 2709–18.

Spectroscopic studies reveal that the heme regulatory motifs of heme oxygenase-2 are dynamically disordered and exhibit redox-dependent interaction with heme.
Bagai I, Sarangi R, Fleischhacker AS, Sharma A, Hoffman BM, Zuiderweg ER, Ragsdale SW.
Biochemistry. 2015; 54: 2693–708.

The reaction mechanism of methyl-coenzyme M reductase: how an enzyme enforces strict binding order.
Wongnate T, Ragsdale SW.
J Biol Chem. 2015; 290: 9322–34.


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.
Ragsdale SW.
Met Ions Life Sci. 2014; 14: 125–45.

Investigations of the efficient electrocatalytic interconversions of carbon dioxide and carbon monoxide by nickel-containing carbon monoxide dehydrogenases.
Wang VC, Ragsdale SW, Armstrong FA.
Met Ions Life Sci. 2014; 14: 71–97.

Selective visible-light-driven CO2 reduction on a p-type dye-sensitized NiO photocathode.
Bachmeier A, Hall S, Ragsdale SW, Armstrong FA.
J Am Chem Soc. 2014; 136: 13518–21.

Protein/protein interactions in the mammalian heme degradation pathway: heme oxygenase-2, cytochrome P450 reductase, and biliverdin reductase.
Spencer AL, Bagai I, Becker DF, Zuiderweg ER, Ragsdale SW.
J Biol Chem. 2014; 289: 29836–58.

Structure, function, and mechanism of the nickel metalloenzymes, CO dehydrogenase, and acetyl-CoA synthase.
Can M, Armstrong FA, Ragsdale SW.
Chem Rev. 2014; 114: 4149–74.

Modulation of nuclear receptor function by cellular redox poise.
Carter EL, Ragsdale SW.
J Inorg Biochem. 2014; 133: 92–103.

How light-harvesting semiconductors can alter the bias of reversible electrocatalysts in favor of H2 production and CO2 reduction.
Bachmeier A, Wang VC, Woolerton TW, Bell S, Fontecilla-Camps JC, Can M, Ragsdale SW, Chaudhary YS, Armstrong FA.
J Am Chem Soc. 2013; 135: 15026–32.

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

Frontiers, opportunities, and challenges in biochemical and chemical catalysis of CO2 fixation.
Appel AM, Bercaw JE, Bocarsly AB, Dobbek H, DuBois DL, Dupuis M, Ferry JG, Fujita E, Hille R, Kenis PJ, Kerfeld CA, Morris RH, Peden CH, Portis AR, Ragsdale SW, Rauchfuss TB, Reek JN, Seefeldt LC, Thauer RK, Waldrop GL.
Chem Rev. 2013; 113: 6621–58.

In vivo activation of methyl-coenzyme M reductase by carbon monoxide.
Zhou Y, Dorchak AE, Ragsdale SW.
Front Microbiol. 2013; 4: 69.

A unified electrocatalytic description of the action of inhibitors of nickel carbon monoxide dehydrogenase.
Wang VC, Can M, Pierce E, Ragsdale SW, Armstrong FA.
J Am Chem Soc. 2013; 135: 2198–206.

CO Dehydrogenase/Acetyl-CoA Synthase.
Ragsdale SW, Pierce E, Bender, G.
In Encyclopedia of Metalloproteins (Springer) 2013; 691–700.

Thiol/Disulfide Redox Switches as a Regulatory Mechanism in Heme-binding Proteins.
Ragsdale SW, Gupta N, Bagai I, Spencer, AM, Carter E.
In Handbook of Porphyrin Science, Volume 30 (World Scientific) 2013; 31–54.


Transient B12-dependent methyltransferase complexes revealed by small-angle X-ray scattering.
Ando N, Kung Y, Can M, Bender G, Ragsdale SW, Drennan CL.
J Am Chem Soc. 2012; 134: 17945–54.

Redox, haem and CO in enzymatic catalysis and regulation.
Ragsdale SW, Yi L, Bender G, Gupta N, Kung Y, Yan L, Stich TA, Doukov T, Leichert L, Jenkins PM, Bianchetti CM, George SJ, Cramer SP, Britt RD, Jakob U, Martens JR, Phillips GN Jr, Drennan CL.
Biochem Soc Trans. 2012; 40: 501–7.

Visualizing molecular juggling within a B12-dependent methyltransferase complex.
Kung Y, Ando N, Doukov TI, Blasiak LC, Bender G, Seravalli J, Ragsdale SW, Drennan CL.
Nature. 2012; 484: 265–9.

Radical reactions of thiamin pyrophosphate in 2-oxoacid oxidoreductases.
Reed GH, Ragsdale SW, Mansoorabadi SO.
Biochim Biophys Acta. 2012; 1824: 1291–8.

Visible light-driven CO2 reduction by enzyme coupled CdS nanocrystals.
Chaudhary YS, Woolerton TW, Allen CS, Warner JH, Pierce E, Ragsdale SW, Armstrong FA.
Chem Commun (Camb). 2012; 48: 58–60.

Metal centers in the anaerobic microbial metabolism of CO and CO2.
Bender G, Pierce E, Hill JA, Darty JE, Ragsdale SW.
Metallomics. 2011; 3: 797–815.

Biochemistry of Methyl-CoM Reductase and Coenzyme F430.
Zhou Y, Sliwa DA, Ragsdale SW.
In Handbook of Porphyrin Science, Volume 19 (World Scientific) 2012; 86: 1–44.

Preface to Methods in Methane Metabolism, Part A: Methanogenesis.
Rosenzweig AC, Ragsdale SW.
Methods Enzymol. 2011; 494: xv–xvi.

Preface to Methods in Methane Metabolism, Part B: Methanotrophy.
Rosenzweig AC, Ragsdale SW.
Methods Enzymol. 2011; 495: xv–xvi.

Pseudo-4D triple resonance experiments to resolve HN overlap in the backbone assignment of unfolded proteins.
Bagai I, Ragsdale SW, Zuiderweg ER.
J Biomol NMR. 2011; 49: 69–74.

Biochemistry: How two amino acids become one.
Ragsdale SW.
Nature. 2011; 471: 583–4.

Thiol/Disulfide redox switches in the regulation of heme binding to proteins.
Ragsdale SW, Yi L.
Antioxid Redox Signal. 2011; 14: 1039–47.

CO2 photoreduction at enzyme-modified metal oxide nanoparticles.
Woolerton TW, Sheard S, Pierce E, Ragsdale SW, Armstrong FA.
Energy Environ Sci. 2011; 4: 2393–9.

Structural analysis of a Ni-methyl species in methyl-coenzyme M reductase from Methanothermobacter marburgensis.
Cedervall PE, Dey M, Li X, Sarangi R, Hedman B, Ragsdale SW, Wilmot CM.
J Am Chem Soc. 2011; 133: 5626–8.

Thiol-disulfide redox dependence of heme binding and heme ligand switching in nuclear hormone receptor rev-erb{beta}.
Gupta N, Ragsdale SW.
J Biol Chem. 2011; 286: 4392–403.

Evidence that ferredoxin interfaces with an internal redox shuttle in Acetyl-CoA synthase during reductive activation and catalysis.
Bender G, Ragsdale SW.
Biochemistry. 2011; 50: 276–86.


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 analogue.
Dey M, Li X, Kunz RC, Ragsdale SW.
Biochemistry. 2010; 49: 10902–11.

Identification and characterization of oxalate oxidoreductase, a novel thiamine pyrophosphate-dependent 2-oxoacid oxidoreductase that enables anaerobic growth on oxalate.
Pierce E, Becker DF, Ragsdale SW.
J Biol Chem. 2010; 285: 40515–24.

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.
Bender G, Stich TA, Yan L, Britt RD, Cramer SP, Ragsdale SW.
Biochemistry. 2010; 49: 7516–23.

Structural insight into methyl-coenzyme M reductase chemistry using coenzyme B analogues.
Cedervall PE, Dey M, Pearson AR, Ragsdale SW, Wilmot CM.
Biochemistry. 2010; 49: 7683–93.

Observation of organometallic and radical intermediates formed during the reaction of methyl-coenzyme M reductase with bromoethanesulfonate.
Li X, Telser J, Kunz RC, Hoffman BM, Gerfen G, Ragsdale SW.
Biochemistry. 2010; 49: 6866–76.

Identification of a thiol/disulfide redox switch in the human BK channel that controls its affinity for heme and CO.
Yi L, Morgan JT, Ragsdale SW.
J Biol Chem. 2010; 285: 20117–27.

Spectroscopic insights into axial ligation and active-site H-bonding in substrate-bound human heme oxygenase-2.
Gardner JD, Yi L, Ragsdale SW, Brunold TC.
J Biol Inorg Chem. 2010; 15: 1117–27.

Efficient and clean photoreduction of CO2 to CO by enzyme-modified TiO2 nanoparticles using visible light.
Woolerton TW, Sheard S, Reisner E, Pierce E, Ragsdale SW, Armstrong FA.
J Am Chem Soc. 2010; 132: 2132–3.

Expanding the biological periodic table.
Seravalli J, Ragsdale SW.
Chem Biol. 2010; 17: 793–4.

Evidence for organometallic intermediates in bacterial methane formation involving the nickel coenzyme F430.
Dey M, Li X, Zhou Y, Ragsdale SW.
Met Ions Life Sci. 2010; 7: 71–110.

Function of Ech hydrogenase in ferredoxin-dependent, membrane-bound electron transport in Methanosarcina mazei.
Welte C, Kallnik V, Grapp M, Bender G, Ragsdale S, Deppenmeier U.
J Bacteriol. 2010; 192: 674–8.

Nickel-Based Enzyme Systems.
Ragsdale SW.
J Biol Chem. 2009; 284: 18571–5.

Water-gas shift reaction catalyzed by redox enzymes on conducting graphite platelets.
Lazarus O, Woolerton TW, Parkin A, Lukey MJ, Reisner E, Seravalli J, Pierce E, Ragsdale SW, Sargent F, Armstrong FA.
J Am Chem Soc. 2009; 131: 14154–5.

Crystallographic snapshots of cyanide- and water-bound C-clusters from bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase.
Kung Y, Doukov TI, Seravalli J, Ragsdale SW, Drennan CL.
Biochemistry. 2009; 48: 7432–40.

Heme regulatory motifs in heme oxygenase-2 form a thiol/disulfide redox switch that responds to the cellular redox state.
Yi L, Jenkins PM, Leichert LI, Jakob U, Martens JR, Ragsdale SW.
J Biol Chem. 2009; 284: 20556–61.

Geometric and electronic structures of the Ni(I) and methyl-Ni(III) intermediates of methyl-coenzyme M reductase.
Sarangi R, Dey M, Ragsdale SW.
Biochemistry. 2009; 48: 3146–56.


Acetogenesis and the Wood-Ljungdahl pathway of CO2 fixation.
Ragsdale SW, Pierce E.
Biochim Biophys Acta. 2008; 1784: 1873–98.

Dual roles of an essential cysteine residue in activity of a redox-regulated bacterial transcriptional activator.
Gupta N, Ragsdale SW.
J Biol Chem. 2008; 283: 28721–8.

13C NMR characterization of an exchange reaction between CO and CO2 catalyzed by carbon monoxide dehydrogenase.
Seravalli J, Ragsdale SW.
Biochemistry. 2008; 47: 6770–81.

The complete genome sequence of Moorella thermoacetica (f. Clostridium thermoaceticum).
Pierce E, Xie G, Barabote RD, Saunders E, Han CS, Detter JC, Richardson P, Brettin TS, Das A, Ljungdahl LG, Ragsdale SW.
Environ Microbiol. 2008; 10: 2550–73.

Enzymology of the wood-Ljungdahl pathway of acetogenesis.
Ragsdale SW.
Ann N Y Acad Sci. 2008; 1125: 129–36.

Xenon in and at the end of the tunnel of bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase.
Doukov TI, Blasiak LC, Seravalli J, Ragsdale SW, Drennan CL.
Biochemistry. 2008; 47: 3474–83.

Characterization of the thioether product formed from the thiolytic cleavage of the alkyl-nickel bond in methyl-coenzyme M reductase.
Kunz RC, Dey M, Ragsdale SW.
Biochemistry. 2008; 47: 2661–7.

Pulse-chase studies of the synthesis of acetyl-CoA by carbon monoxide dehydrogenase/acetyl-CoA synthase: evidence for a random mechanism of methyl and carbonyl addition.
Seravalli J, Ragsdale SW.
J Biol Chem. 2008; 283: 8384–94.

Catalysis of methyl group transfers involving tetrahydrofolate and B(12).
Ragsdale SW.
Vitam Horm. 2008; 79: 293–324.

Heme Oxygenase.
Ragsdale SW.
in Redox Biochemistry (Wiley). 2008; Ch. 3.7.B: 131–4.

Redox Enzymology.
Ragsdale SW.
in Redox Biochemistry (Wiley). 2008; Ch. 4.6: 173–7.

Electron Paramagnetic Resonance (EPR) for the Redox Biochemist.
Ragsdale SW, Seravalli J.
in Redox Biochemistry (Wiley). 2008; Ch. 6.2: 237–47.

Comparison of apo- and heme-bound crystal structures of a truncated human heme oxygenase-2.
Bianchetti CM, Yi L, Ragsdale SW, Phillips GN Jr.
J Biol Chem. 2007; 282: 37624–31.

Characterization of alkyl-nickel adducts generated by reaction of methyl-coenzyme m reductase with brominated acids.
Dey M, Kunz RC, Lyons DM, Ragsdale SW.
Biochemistry. 2007; 46: 11969–78.

Biochemical and spectroscopic studies of the electronic structure and reactivity of a methyl-Ni species formed on methyl-coenzyme M reductase.
Dey M, Telser J, Kunz RC, Lees NS, Ragsdale SW, Hoffman BM.
J Am Chem Soc. 2007; 129: 11030–2.

Rapid and efficient electrocatalytic CO2/CO interconversions by Carboxydothermus hydrogenoformans CO dehydrogenase I on an electrode.
Parkin A, Seravalli J, Vincent KA, Ragsdale SW, Armstrong FA.
J Am Chem Soc. 2007; 129: 10328–9.

Nickel and the carbon cycle.
Ragsdale SW.
J Inorg Biochem. 2007; 101: 1657–66.

Evidence that the heme regulatory motifs in heme oxygenase-2 serve as a thiol/disulfide redox switch regulating heme binding.
Yi L, Ragsdale SW.
J Biol Chem. 2007; 282: 21056–67.

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.
Doukov TI, Hemmi H, Drennan CL, Ragsdale SW.
J Biol Chem. 2007; 282: 6609–18.

Metalloenzymes in the Reduction of One-Carbon Compounds.
Ragsdale SW.
in Biological Inorganic Chemistry: Structure and Reactivity (University Science Books). 2007; Ch. 12.2: 452–67.

Selected 1999–2006

Spectroscopic and kinetic studies of the reaction of bromopropanesulfonate with methyl-coenzyme M reductase.
Kunz RC, Horng YC, Ragsdale SW.
J Biol Chem. 2006; 281: 34663–76.

Spectroscopic and computational studies of reduction of the metal versus the tetrapyrrole ring of coenzyme F430 from methyl-coenzyme M reductase.
Dey M, Kunz RC, Van Heuvelen KM, Craft JL, Horng YC, Tang Q, Bocian DF, George SJ, Brunold TC, Ragsdale SW.
Biochemistry. 2006; 45: 11915–33.

Transcriptional activation of dehalorespiration. Identification of redox-active cysteines regulating dimerization and DNA binding.
Pop SM, Gupta N, Raza AS, Ragsdale SW.
J Biol Chem. 2006; 281: 26382–90.

CprK crystal structures reveal mechanism for transcriptional control of halorespiration.
Joyce MG, Levy C, Gábor K, Pop SM, Biehl BD, Doukov TI, Ryter JM, Mazon H, Smidt H, van den Heuvel RH, Ragsdale SW, van der Oost J, Leys D.
J Biol Chem. 2006; 281: 28318–25.

EPR spectroscopic and computational characterization of the hydroxyethylidene-thiamine pyrophosphate radical intermediate of pyruvate:ferredoxin oxidoreductase.
Mansoorabadi SO, Seravalli J, Furdui C, Krymov V, Gerfen GJ, Begley TP, Melnick J, Ragsdale SW, Reed GH.
Biochemistry. 2006; 45: 7122–31.

Pulsed electron paramagnetic resonance experiments identify the paramagnetic intermediates in the pyruvate ferredoxin oxidoreductase catalytic cycle.
Astashkin AV, Seravalli J, Mansoorabadi SO, Reed GH, Ragsdale SW.
J Am Chem Soc. 2006; 128: 3888–9.

Spectroscopic studies of the corrinoid/iron-sulfur protein from Moorella thermoacetica.
Stich TA, Seravalli J, Venkateshrao S, Spiro TG, Ragsdale SW, Brunold TC.
J Am Chem Soc. 2006; 128: 5010–20.

Reduction and oxidation of the active site iron in tyrosine hydroxylase: kinetics and specificity.
Frantom PA, Seravalli J, Ragsdale SW, Fitzpatrick PF.
Biochemistry. 2006; 45: 2372–9.

Metals and their scaffolds to promote difficult enzymatic reactions.
Ragsdale SW.
Chem Rev. 2006; 106: 3317–37.

EPR and infrared spectroscopic evidence that a kinetically competent paramagnetic intermediate is formed when acetyl-coenzyme A synthase reacts with CO.
George SJ, Seravalli J, Ragsdale SW.
J Am Chem Soc. 2005; 127: 13500–1.

Regulation of anaerobic dehalorespiration by the transcriptional activator CprK.
Pop SM, Kolarik RJ, Ragsdale SW.
J Biol Chem. 2004; 279: 49910–18.

Mechanism of 4-(beta-D-ribofuranosyl)aminobenzene 5'-phosphate synthase, a key enzyme in the methanopterin biosynthetic pathway.
Dumitru RV, Ragsdale SW.
J Biol Chem. 2004; 279: 39389–95.

Nickel oxidation states of F430 cofactor in methyl-coenzyme M reductase.
Craft JL, Horng YC, Ragsdale SW, Brunold TC.
J Am Chem Soc. 2004; 126: 4068–9.

CO-induced structural rearrangement of the C cluster in Carboxydothermus hydrogenoformans CO dehydrogenase-evidence from Ni K-edge X-ray absorption spectroscopy.
Gu W, Seravalli J, Ragsdale SW, Cramer SP.
Biochemistry. 2004; 43: 9029–35.

Evidence that NiNi acetyl-CoA synthase is active and that the CuNi enzyme is not.
Seravalli J, Xiao Y, Gu W, Cramer SP, Antholine WE, Krymov V, Gerfen GJ, Ragsdale SW.
Biochemistry. 2004; 43: 3944–55.

Spectroscopic and computational characterization of the nickel-containing F430 cofactor of methyl-coenzyme M reductase.
Craft JL, Horng YC, Ragsdale SW, Brunold TC.
J Biol Inorg Chem. 2004; 9: 77–89.

Infrared studies of carbon monoxide binding to carbon monoxide dehydrogenase/acetyl-CoA synthase from Moorella thermoacetica.
Chen J, Huang S, Seravalli J, Gutzman H Jr, Swartz DJ, Ragsdale SW, Bagley KA.
Biochemistry. 2003; 42: 14822–30.

Targeting methanopterin biosynthesis to inhibit methanogenesis.
Dumitru R, Palencia H, Schroeder SD, DeMontigny BA, Takacs JM, Rasche ME, Miner JL, Ragsdale SW.
Appl Environ Microbiol. 2003; 69: 7236–41.

Rapid ligand exchange in the MCRred1 form of methyl-coenzyme M reductase.
Singh K, Horng YC, Ragsdale SW.
J Am Chem Soc. 2003; 125: 2436–43.

Functional copper at the acetyl-CoA synthase active site.
Seravalli J, Gu W, Tam A, Strauss E, Begley TP, Cramer SP, Ragsdale SW.
Proc Natl Acad Sci U S A. 2003; 100: 3689–94.

A Ni-Fe-Cu center in a bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase.
Doukov TI, Iverson TM, Seravalli J, Ragsdale SW, Drennan CL.
Science. 2002; 298: 567–72.

X-ray absorption and resonance Raman studies of methyl-coenzyme M reductase indicating that ligand exchange and macrocycle reduction accompany reductive activation.
Tang Q, Carrington PE, Horng YC, Maroney MJ, Ragsdale SW, Bocian DF.
J Am Chem Soc. 2002; 124: 13242–56.

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.
Furdui C, Ragsdale SW.
Biochemistry. 2002; 41: 9921–37.

Rapid kinetic studies of acetyl-CoA synthesis: evidence supporting the catalytic intermediacy of a paramagnetic NiFeC species in the autotrophic Wood-Ljungdahl pathway.
Seravalli J, Kumar M, Ragsdale SW.
Biochemistry. 2002; 41: 1807–19.

Redox centers of 4-hydroxybenzoyl-CoA reductase, a member of the xanthine oxidase family of molybdenum-containing enzymes.
Boll M, Fuchs G, Meier C, Trautwein A, El Kasmi A, Ragsdale SW, Buchanan G, Lowe DJ.
J Biol Chem. 2001; 276: 47853–62.

Acetyl coenzyme A synthesis from unnatural methylated corrinoids: requirement for "base-off" coordination at cobalt.
Seravalli J, Brown KL, Ragsdale SW.
J Am Chem Soc. 2001; 123: 1786–7.

Characterization of the intramolecular electron transfer pathway from 2-hydroxyphenazine to the heterodisulfide reductase from Methanosarcina thermophila.
Murakami E, Deppenmeier U, Ragsdale SW.
J Biol Chem. 2001; 276: 2432–9.

Characterization of a three-component vanillate O-demethylase from Moorella thermoacetica.
Naidu D, Ragsdale SW.
J Bacteriol. 2001; 183: 3276–81.

Cryoreduction of methyl-coenzyme M reductase: EPR characterization of forms, MCR(ox1) and MCR (red1).
Telser J, Davydov R, Horng YC, Ragsdale SW, Hoffman BM.
J Am Chem Soc. 2001; 123: 5853–60.

Mechanistic studies of methane biogenesis by methyl-coenzyme M reductase: evidence that coenzyme B participates in cleaving the C-S bond of methyl-coenzyme M.
Horng YC, Becker DF, Ragsdale SW.
Biochemistry. 2001; 40: 12875–85.

Characterization of the B12- and iron-sulfur-containing reductive dehalogenase from Desulfitobacterium chlororespirans.
Krasotkina J, Walters T, Maruya KA, Ragsdale SW.
J Biol Chem. 2001; 276: 40991–7.

Channeling of carbon monoxide during anaerobic carbon dioxide fixation.
Seravalli J, Ragsdale SW.
Biochemistry. 2000; 39: 1274–7.

On the assignment of nickel oxidation states of the Ox1, Ox2 Forms of Methyl-Coenzyme M Reductase.
Telser J, Horng YC, Becker DF, Hoffman BM, Ragsdale SW.
J Am Chem Soc. 2000; 122: 182–3.

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.
Murakami E, Ragsdale SW.
J Biol Chem. 2000; 275: 4699–707.

Crystal structure of a methyltetrahydrofolate- and corrinoid-dependent methyltransferase.
Doukov T, Seravalli J, Stezowski JJ, Ragsdale SW.
Structure. 2000; 8: 817–30.

The role of pyruvate ferredoxin oxidoreductase in pyruvate synthesis during autotrophic growth by the Wood-Ljungdahl pathway.
Furdui C, Ragsdale SW.
J Biol Chem. 2000; 275: 28494–9.

Characterization of heterogeneous nickel sites in CO dehydrogenases from Clostridium thermoaceticum and Rhodospirillum rubrum by nickel L-edge X-ray spectroscopy.
Ralston CY, Wang H, Ragsdale SW, Dumar M, Spangler NJ, Ludden PW, Gu W, Jones RM, Patil DS, Cramer SP.
J Am Chem Soc. 2000; 122: 10553–60.

Nitrate-dependent regulation of acetate biosynthesis and nitrate respiration by Clostridium thermoaceticum.
Arendsen AF, Soliman MQ, Ragsdale SW.
J Bacteriol. 1999; 181: 1489–95.

ENDOR studies of pyruvate: ferredoxin oxidoreductase reaction intermediates.
Bouchev VF, Furdui CM, Menon S, Muthukumaran RB, Ragsdale SW, McCracken J.
J Am Chem Soc. 1999; 121: 3724–9.

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.
Seravalli J, Zhao S, Ragsdale SW.
Biochemistry. 1999; 38: 5728–35.

Binding of (6R,S)-methyltetrahydrofolate to methyltransferase from Clostridium thermoaceticum: role of protonation of methyltetrahydrofolate in the mechanism of methyl transfer.
Seravalli J, Shoemaker RK, Sudbeck MJ, Ragsdale SW.
Biochemistry. 1999; 38: 5736–45.

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.
Menon S, Ragsdale SW.
J Biol Chem. 1999; 274: 11513–8.

Older Invited Review Articles

The metalloclusters of carbon monoxide dehydrogenase/acetyl-CoA synthase: a story in pictures.
Drennan CL, Doukov TI, Ragsdale SW.
J Biol Inorg Chem. 2004; 9: 511–5.

Life with carbon monoxide.
Ragsdale SW.
Crit Rev Biochem Mol Biol. 2004; 39: 165–95.

The many faces of vitamin B12: catalysis by cobalamin-dependent enzymes.
Banerjee R, Ragsdale SW.
Annu Rev Biochem. 2003; 72: 209–47.

Pyruvate ferredoxin oxidoreductase and its radical intermediate.
Ragsdale SW.
Chem Rev. 2003; 103: 2333–46.

Biochemistry of Methyl-CoM Reductase and Coenzyme F430.
Ragsdale SW.
In The Porphyrin Handbook, Volume 11: Bioinorganic and Bioorganic Chemistry (Academic Press). 2003; Ch. 67: 205–28.

Biocatalytic One-Carbon Conversion.
Ragsdale SW.
In Encyclopedia of Catalysis (Wiley). 2002; 665–95.

Nickel Containing CO Dehydrogenases and Hydrogenases.
Ragsdale SW.
In Enzyme-Catalyzed Electron and Radical Transfer (Plenum). 2000; 487–518.

Nickel-Iron-Sulfur Active Sites: Hydrogenase and CO Dehydrogenase.
Fontecilla-Camps JC, Ragsdale SW.
In Advances in Inorganic Chemistry, Volume 47 (Academic Press). 1999; 283–333.

The Acetogenic Corrinoid Proteins.
Ragsdale SW.
In Chemistry and Biochemistry of B12 (Wiley). 1999; 633–54.

For a list of publications from Pubmed, click HERE

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