Research in this laboratory is concerned with structural and functional aspects of two related areas: (1) catalysis done by ribonucleic acid (RNA) enzymes and (2) catalysis done on RNA by protein enzymes. These two areas touch upon mechanisms that are critical in translation of genetic information, evolution of biocatalysts and how chemistry is performed by two different types of macromolecules.

RNA is postulated to have preceded proteins as biocatalyst in the hypothetical primordial RNA world. RNA can perform biochemical catalysis and should, in principle, be able to catalyze most reactions currently catalyzed by proteins. Our laboratory is using x-ray crystallographic approaches to characterize the structural and functional parameters of catalytic RNA at the atomic level and to examine how these enzymes recognize their substrates and perform their catalytic functions, and we are employing biochemical approaches to modify these functions through structure-based RNA design.

Protein enzymes acting on RNA play important roles in a number of cellular processes, most notably in protein biosynthesis and RNA processing. They are also potential drug targets. Our laboratory is using x-ray crystallography to characterize how these enzymes recognize the general shape of their RNA substrates or substructures thereof and how they perform their functions. Furthermore, to examine the structure-function relationships we use site-directed mutagenesis followed by biochemical and structural analyses.

Students in this laboratory can receive training in developing expression systems, preparation of RNA and proteins, crystallization of single components and complexes, x-ray data collection using rotating anode and synchrotron sources, and determination, refinement and analysis of crystal structures.
 

Differential influence of nucleoside analog-resistance mutations K65R and L74V on the overall mutation rate and error specificity of human immunodeficiency virus type 1 reverse transcriptase
Shah, F.S., Curr, K.A., Hamburgh, M.E., Parniak, M., Mitsuya,
H., Arnez, J.G. and Prasad, V.R.
J. Biol. Chem. 2000,  275, 27037-27044.

Aminoacylation at the atomic level in class IIa aminoacyl-tRNA synthetases
Arnez, J.G., Sankaranarayanan, R., Dock-Bregeon, A.-C.,
Francklyn, C.S. and Moras, D.
J. Biomolec. Struct. & Dyn. Conversation 11, Number 1, 23-28.

Glycyl-tRNA synthetase uses a negatively charged pit for specific
recognition and activation of glycine
 Arnez, J.G., Dock-Bregeon, A.-C. and Moras, D.
J. Mol. Biol. 1999, 286, 1449-1459, Abstract

Application of the molecular replacement method to a heavy atom problem
J. Appl. Cryst. 1999, 32, 472-474, Abstract

Histidyl-tRNA synthetase
Freist, W., Verhey, J.F., Rühlmann, A., Gauss, D.H. and Arnez, J.G.
Biol. Chem., 1999, 380, 623-646

Aminoacyl-tRNA synthetases In: Encyclopedia of Life Sciences
Arnez, J.G. and Moras, D.
Ed. S. Robertson,  Macmillan, Reference Ltd., London, 1999

Transfer RNA In: Oxford Handbook of Nucleic Acid Structure
Arnez, J.G. and Moras, D.
Ed. S. Neidle, Oxford University Press, Oxford, pp. 603-651, 1999