Stephen Wiley Ragsdale
University of Michigan, MI·Biochemistry
Metal atoms inside proteins carry out some of biology's hardest chemistry. They fix carbon dioxide in ancient microbes, break down heme (the iron-containing molecule in blood) in humans, and convert mercury into a more toxic form in the environment.
- Fields
Biochemistry
Chemistry
Biophysics
- Topics
metalloproteins
bioinorganic chemistry
enzyme mechanisms
- Grants
- 2 known grants, through Jun 2027
What they work on
- Determine how the heme oxygenase-2 (HO2) catalytic core coordinates heme sequestration with its own lysosomal breakdown during heme deficiency, and test whether inducible HO1 also sequesters heme.
- Test whether the heme chaperone GAPDH transfers heme directly to HO2's catalytic core or to its tail, which carries heme regulatory motifs (HRMs), and whether these motifs shuttle heme in cells.
- Compare full-length, membrane-anchored HO2 in nanodiscs and liposomes with the soluble protein, including its interactions with its electron donor, cytochrome P450 reductase.
- Trace how Rev-Erbβ, a gene-repressing protein tied to the circadian clock, is regulated from heme loading to CO binding, and whether HO passes CO to it directly through a protein complex.
- Define how Wood-Ljungdahl pathway enzymes generate and use CO, including organometallic intermediates, domain movements and an interprotein CO channel, during anaerobic CO2 fixation.
- Determine the structure of the mercury-methylating HgcAB complex and whether its B12 and iron-sulfur centers transfer a methyl radical or a methyl anion.
More about the research
This work studies how these metalloproteins, proteins built around metal centers, catalyze reactions and how their activity is controlled by redox state, meaning the gain or loss of electrons. The approaches span biology, biophysics, biochemistry and computation. The research falls into three areas: human heme and carbon monoxide (CO) signaling, microbial carbon fixation, and microbial mercury methylation.
Why it matters
Heme oxygenases protect cells against oxidative stress linked to heart, kidney and nervous-system diseases. Rev-Erbβ dysfunction is associated with metabolic, circadian and inflammatory disorders, and abnormal circadian rhythms are associated with cancer. Understanding these proteins could inform those conditions. The microbial enzyme studies could guide chemists making fuels from CO2 and methane, and clarify how microbes produce toxic methylmercury in the environment.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Joseph M Bollinger
Pennsylvania State University, PA·Biochemistry
Determine how iron(II) and 2-oxoglutarate-dependent (Fe/2OG) oxygenases direct a common oxoiron(IV) intermediate toward hydroxylation, halogenation, desaturation, or cyclization, and test this by rationally redirecting reaction outcomes.
Ambika Bhagi
University of Minnesota, MN·Biochemistry
Use structure-guided protein design to reprogram how sensitive and selective the heme iron sensor enzymes DosS and DosT are to low oxygen, nitric oxide and carbon monoxide.
Gayan Wijeratne
University of Alabama, AL·Chemistry
Synthesize heme-nitrogen oxide model complexes with systematically varied ligands in the primary and secondary coordination spheres, to find which features of the heme center control the geometry and electronic structure of these intermediates.
The school
University of Michigan: 124 labs on PI Pages, $2.1B a year on research, 963 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.