February 2011

Ruma V. Banerjee and Stephen W. Ragsdale: deciphering sulfur and carbon metabolism

Ragsdale has expanded his field of research to include methanogenesis in addition to acetogenesis, and his group recently elucidated the reaction for the final step in methane synthesis, demonstrating that the process is nickel-dependent.

“I’ve been getting excited about that area because not only does methane have many wonderful chemical properties, but it could be a great source of future energy,” Ragsdale says. “There’s lots of stored methane available, it’s got a great energy potential and it’s clean burning.”

Following an eye-opening Gordon Conference on metals in biology, the formerly inorganic-adverse Ragsdale also has become interested in other classes of metalloproteins. One intriguing area his lab has just started investigating involves a potentially novel type of metabolic regulation in which thiol/disulfide redox switches regulate a protein’s affinity for heme; these heme-regulatory motifs respond to conditions like oxidative stress and subsequently adjust protein function. The heme functionality also allows the protein to respond to gas-signaling molecules like carbon monoxide and nitric oxide.

And, in a discovery that definitely pleased his music-loving soul, Ragsdale even found one such thiol/disulfide redox switch on a key nuclear hormone receptor involved in the circadian cycle called Rev-erb. “It was not a planned occurrence, and I didn’t name the protein,” he says, “but it kind of highlights the wonders of science and how the right protein, or person, seems to find you.”

References

Banerjee, R. V., Harder, S. R., Ragsdale, S. W., and Matthews, R. G. (1990) Mechanism of reductive activation of cobalamin-dependent methionine synthase: an electron paramagnetic resonance spectroelectrochemical study. Biochemistry 29, 1129 – 1135.

Kim, J., Gherasim, C., and Banerjee, R. (2008) Decyanation of vitamin B12 by a trafficking chaperone. Proc. Nat. Acad. Sci. 105, 14551 – 14554.

Padovani, D., Labunska, T., Palfey, B. A., Ballou, D. P., and Banerjee, R. (2008) Adenosyltransferase tailors and delivers coenzyme B12. Nature Chem. Biol. 4, 194 – 196.

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.

Gupta, N., and Ragsdale, S. W. (2010) Thiol-disulfide redox dependence of heme binding and heme ligand switching in a nuclear hormone receptor Rev-erb{beta}. J. Biol. Chem. [Epub Dec 1 ahead of print].

Nick Zagorski (nicozags@gmail.com) is a freelance science writer.

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