Profile

Research Interests

Dr. Iwata-Reuyl's research interests are in the area of modern biological chemistry, and include the chemistry and enzymology of RNA modification, the role of modified nucleosides in RNA function, the biosynthetic pathways of secondary metabolism, the molecular genetics of biosynthetic pathways, and protein/nucleic acid interactions. At present his group is investigating the biochemistry of the hypermodified nucleosides queuosine and archaeosine, which are present in specific transfer RNA molecules.

Transfer RNA (tRNA) is structurally unique among nucleic acids in harboring an astonishing diversity of modified nucleosides, many of which are highly conserved in type and location across broad phylogenetic boundaries. Arguably the most remarkable modifications known to occur in tRNA are the hypermodified nucleosides queuosine and archaeosine. Although both nucleosides share an unusual 7-deazaguanosine core structure, they are rigorously segregated with respect to phyla, location in the tRNA, and presumed function; queuosine is ubiquitous throughout the Bacteria and Eukarya where it occurs specifically at the wobble position in a subset of tRNA's. Its location in the anticodon suggests a role in modulating translational fidelity and/or efficiency. Archaeosine is found exclusively in the Archae, and is located at position 15 of the D-loop in the majority of known archaeal tRNA's. Its position at a critical interface of the D-loop and T-stem in the tertiary structure of the tRNA suggests a role in maintaining the structural integrity of the tRNA.

The work currently underway in Dr. Iwata-Reuyl's laboratory is focused on discovering and characterizing the enzymes responsible for the biosynthesis of queuosine and archaeosine, developing an understanding of their biochemical mechanisms, and addressing specific functional questions. These investigations incorporate diverse experimental methodologies, from enzymology and molecular biology, to synthetic and physical organic chemistry.

Representative Publications

• Sankaran, B.; Bonnett, S.; Shah, K.; Gabriel, S.; Reddy, R.; Schimmel, P.; Rodionov, D. A.; de Crécy-Lagard, V.; Helmann, J. D.; Iwata-Reuyl, D.; and Swairjo, M. A. "Zinc-Independent Folate Biosynthesis: Structural, Biochemical and Genetic Investigations Reveal New Metal Dependence for GTP Cyclohydrolase IB," in press, J. Mol. Biol.
• Iwata-Reuyl, D. "An Embarassment of Riches: The enzymology of tRNA modification," Current Opinion in Chemical Biology," 2008, 12, 126-133.
• Lee, B.; Van Lanen, S. G.; Iwata-Reuyl, D. "Mechanistic studies of QueF, the nitrile oxidoreductase involved in the biosynthesis of queuosine," Biochemistry, 2008, 46, 12844-12854.
• Roth, A.; Winkler, W. C.; Regulski, E.; Lee, B.; Lim, J.; Jona, I.; Barrick, J. E.; Ritwik, A.; Kim, J.; Welz, R.; Iwata-Reuyl, D.; Breaker, R. R. "A eubacterial riboswitch selective for the queuosine precursor preQ1 contains an unusually small aptamer domain," Nature Struct. Mol. Biol., 2007, 14, 308-317.
• El Yacoubi, B.; Bonnett, S.; Anderson, J.; Swairjo, M. A.; Iwata-Reuyl, D. and de Crécy-Lagard, V. "Discovery of a new prokaryotic type I GTP cyclohydrolase family," J. Biol. Chem., 2006, 281(49), 37586-37593.
• Van Lanen, S.; Reader, J.S.; Swairjo, M.A.; de Crécy-Lagard, V.; Lee, B.; Iwata-Reuyl, D., "From cyclohydrolase to oxidoreductase: Discovery of nitrile reductase activity in a common fold." Proc. Natl. Acad. Sci. USA, 2005, 102:12, 4264-4269.