| 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.
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"Kinetic Mechanism of the tRNA Modifying Enzyme S-Adenosylmethionine: tRNA Ribosyltransferase-isomerase (QueA)," Van Lanen, S.; Iwata-Reuyl, D., Biochemistry, 2003, 42:18, 5312-5320.
"tRNA Modification by S-Adenosylmethionine:tRNA Ribosyltransferase-isomerase (QueA): Assay Development and Characterization of the Recombinant Enzyme," Van Lanen, S.; Daoud Kinzie, S.; Matthieu, S.; Link, T.; Culp, J.; Iwata-Reuyl, D., J. Biol. Chem., 2003, 278:12, 10491-10499.
"The Biosynthesis of the 7-Deazaguanosine Hypermodified Nucleosides of Transfer RNA," Iwata-Reuyl, D., Bioorg. Chem., 2003, 31, 24-43.
"Mechanistic Studies of the tRNA-Hypermodifying Enzyme QueA: A Chemical Imperative for the Use of AdoMet as a 'Ribosyl' Donor," Daoud Kinzie, S.; Thern, B.; Iwata-Reuyl, D. Org. Lett., 2000, 2, 1307-1310.
"Hypermodification of tRNA in Thermophilic Archae: Cloning, Over-Expression, and Characterization of tRNA-Guanine Transglycosylase from Methanococcus jannaschii," Bai, Y.; Fox, D.; Lacy, J.; Van Lanen, S.; and Iwata-Reuyl, D. J. Biol. Chem., 2000, 275:37, 28731-28738. |
