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Dr. Dirk Iwata-Reuyl
Dr. Dirk Iwata-Reuyl

Professor of Chemistry

Ph.D. | The Johns Hopkins University, 1992

Post-Doctoral Research Fellow 1992-1994, University of Utah


Research Lab Homepage

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

  • Yu, C.H., Luo J., Iwata-Reuyl D., Olsthoorn R.C. “Exploiting preQ(1) Riboswitches To Regulate Ribosomal Frameshifting.” ACS Chem Biol. 2013 Jan 25 PMID: 23327288
  • Chikwana, V. C., Stec, B., Lee, B. W. K., de Crécy-Lagard, V., Iwata-Reuyl, D., Swairjo, M. A. “Structural Basis of Biological Nitrile Reduction.” J. Biol. Chem. 2012, 287(36):30560-70 (PMID: 22787148, PMCID: PMC3436371)
  • Deutsch C., El Yacoubi B., de Crécy-Lagard V., Iwata-Reuyl D. “Biosynthesis of Threonylcarbamoyl Adenosine (t6A), a Universal tRNA Nucleoside.” J. Biol. Chem. 2012, 287(17):13666-73
  • Phillips, G., Swairjo, M.A., Gaston, K. W, Bailly, M., Limbach, P. A., Iwata-Reuyl, D., de Crécy-Lagard, V., “Diversity of Archaeosine Synthesis in Crenarchaeota.” ACS Chem. Biol. 2012, 7(2):300-5.
  • Phillips, G., Grochowski, L. L., Bonnett, S., Xu, H., Bailly, M., Blaby-Haas, C., El Yacoubi, B., Iwata-Reuyl, D., White, R. H., de Crécy-Lagard, V. ”Functional Promiscuity of the COG0720 Family.” ACS Chem. Biol. 2012, 7(1):197-209.
  • Rakovich T., Boland C., Bernstein I., Chikwana V. M., Iwata-Reuyl D., Kelly V. P. “Queuosine deficiency in eukaryotes compromises tyrosine production through increased tetrahydrobiopterin oxidation.” J. Biol. Chem. 2011, 286(22):19354-19363.
  • El Yacoubi, B., Hatin, I., Deutsch, C., Kahveci, T., Rousset, J-P., Iwata-Reuyl, D., Murzin, A., and de Crécy-Lagard, V. “A role for the universal Kae1/Qri7/YgjD (COG0533) family in tRNA modification.” EMBO J. 2011, 30(5):882-893.
  • Phillips, G., Chikwana, V. M., Maxwell, A., El-Yacoubi, B., Swairjo, M. A., Iwata-Reuyl, D. and de Crécy-Lagard, V. “Discovery and characterization of an amidinotransferase involved in the modification of archaeal tRNA.” J. Biol. Chem. 2010, 285:17, 12706-12713.
  • 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.; Swairjo, M. A. "Zinc-independent folate biosynthesis: genetic, biochemical, and structural investigations reveal new metal dependence for GTP Cyclohydrolase IB," J. Bacteriol., 2009, 191, 6939-6949.
  • Iwata-Reuyl, D., and de Crécy-Lagard, V. 2009. "Enzymatic Formation of the 7-Deazaguanosine Hypermodified Nucleosides of tRNA," pp. 377-391. InDNA and RNA Modification Enzymes: Structure, Mechanism, Function and Evolution, Henri Grosjean, Ed. Landes Bioscience, Austin, Tx.
  • Phillips, G.; El Yacoubi, B.; Lyons, B.; Alvarez, S.; Iwata-Reuyl, D.; de Crécy-Lagard, V. "The biosynthesis of the 7-deazaguanosine modified tRNA nucleosides: a new role for GTP cyclohydrolase I," J. Bacteriol., 2008, 190, 7876-7884.
  • Iwata-Reuyl, D. "An Embarrassment 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.