ordered in the absence of DNA. Electron density for 
the DNA has not yet been interpreted unambigu- 
ously. 
II. Protein-RNA Interaction. 
The crystal structure of E. coli glutaminyl-tRNA 
synthetase (GlnRS) complexed with its cognate 
tRNA^'" and ATP has been solved at 2.8 A resolu- 
tion. The enzyme consists of four domains arranged 
to give an elongated molecule with an axial ratio 
> 3 to 1. Its interactions with the tRNA extend from 
the anticodon to the acceptor stem along the en- 
tire inside of the "L" of the tRNA. The complexed 
tRNA retains the overall conformation of the yeast 
tRNA*"*^*^, with two major differences: the 3' accep- 
tor strand of tRNA^'" hairpins back toward the in- 
side of the "L" with the disruption of the final base 
pair of the acceptor stem, and the anticodon loop 
adopts a conformation not seen in any of the pre- 
viously determined tRNA structures. Specific recog- 
nition elements identified so far involve 1) enzyme 
contacts with the two-amino groups of guanine via 
the tRNA minor groove in the acceptor stem at G2 
and G3, 2) interactions between the enzyme and 
the anticodon nucleotides, and 3) the ability of the 
nucleotides G^^ and M^-K^^ of the cognate tRNA to 
assume a conformation stabilized by the protein at 
a lower free-energy cost than noncognate se- 
quences. 
The central domain of this synthetase binds ATP, 
glutamine, and the acceptor end of the tRNA as 
well as making specific interactions with the accep- 
tor stem. It exhibits a strong structural similarity to 
the dinucleotide-binding motifs of the tyrosyl- and 
PUBLICATIONS 
methionyl-tRNA synthetases, suggesting that all syn- 
thetases may have evolved from a common domain 
of this type capable of recognizing the acceptor 
stem of the cognate tRNA. 
III. Human Immunodeficiency Virus (HIV) Proteins. 
HIV reverse transcriptase has been purified from 
an E. coli expression system. Specific tRNA primed 
initiation from RNA and DNA templates is being 
studied to define a system suitable for cocrystalliza- 
tion of protein complexed with tRNA and an appro- 
priate template. 
HIV Tat protein has been expressed as a fusion 
with the cAMP-binding domain of CAP. Both the pu- 
rified chimera and the cleaved Tat bind TAR (trans- 
activation responsive region) RNA quantitatively 
and specifically. Having now established that Tat 
may function by binding to TAR RNA, Dr. Steitz and 
his colleagues will cocrystallize the protein-RNA 
complex. 
IV Other Enzymes. 
Work on the structure of yeast hexokinase in Dr. 
Steitz's laboratory in the 1970s showed that the 
binding of glucose produced a large and essential 
conformational change. Study of the ternary com- 
plex of this enzyme with glucose and ATP is now 
being undertaken to examine the details of catalysis 
in this enzyme. 
Dr. Steitz is also Professor of Molecular Biophys- 
ics and Biochemistry and of Chemistry at Yale Uni- 
versity. 
Books and Chapters of Books 
Beese, L.S., and Steitz, TA. 1989- Structure oiE. coli DNA polymerase I, large fragment, and its functional im- 
plications. In Nucleic Acids and Molecular Biology (Eckstein, F., and Lilley, D., Eds.). Heidelberg: Springer- 
Verlag, pp 28-43. 
Articles 
DiGabriele, A.D., Sanderson, M.R., and Steitz, TA. 1989. Crystal lattice packing is important in determining 
the bend of a DNA dodecamer containing an adenine tract. Proc Natl Acad Sci USA 86:1816-1820. 
Freemont, PS., Friedman, J.M., Beese, L.S., Sanderson, M.R., and Steitz, TA. 1988. Cocrystal structure of an 
editing complex of Klenow fragment with DNA. Proc Natl Acad Sci USA 85:8924-8928. 
Freemont, PS., and Riiger, W 1988. Crystallization and preliminary X-ray studies of T4 phage 
3-glucosyl transferase. J Mol Biol 203:525-526. 
Rice, PA., and Steitz, TA. 1989. Ribosomal protein L7/L12 has a helix-turn-helix motif similar to that found in 
DNA-binding regulatory proteins. Nucleic Acids Res 17:3757-3762. 
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