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Science 24 April 1998:
Vol. 280. no. 5363, pp. 578 - 582
DOI: 10.1126/science.280.5363.578
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Reports

Enzyme Structure with Two Catalytic Sites for Double-Sieve Selection of Substrate

Osamu Nureki, Dmitry G. Vassylyev, Masaru Tateno, Atsushi Shimada, Takashi Nakama, Shuya Fukai, Mitiko Konno, Tamara L. Hendrickson, Paul Schimmel, Shigeyuki Yokoyama *

High-fidelity transfers of genetic information in the central dogma can be achieved by a reaction called editing. The crystal structure of an enzyme with editing activity in translation is presented here at 2.5 angstroms resolution. The enzyme, isoleucyl-transfer RNA synthetase, activates not only the cognate substrate L-isoleucine but also the minimally distinct L-valine in the first, aminoacylation step. Then, in a second, "editing" step, the synthetase itself rapidly hydrolyzes only the valylated products. For this two-step substrate selection, a "double-sieve" mechanism has already been proposed. The present crystal structures of the synthetase in complexes with L-isoleucine and L-valine demonstrate that the first sieve is on the aminoacylation domain containing the Rossmann fold, whereas the second, editing sieve exists on a globular beta -barrel domain that protrudes from the aminoacylation domain.

O. Nureki, M. Tateno, S. Yokoyama, Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan, and Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama 351-01, Japan.
D. G. Vassylyev, International Institute for Advanced Research, Central Research Laboratories, Matsushita Electric Industrial, 3-4 Hikari-dai, Seika, Kyoto 619-02, Japan.
A. Shimada, T. Nakama, S. Fukai, Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.
M. Konno, Department of Chemistry, Faculty of Science, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112, Japan.
T. L. Hendrickson and P. Schimmel, Skaggs Institute for Chemical Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037.
*   To whom correspondence should be addressed. E-mail: yokoyama{at}y-sun.biochem.s.u-tokyo.ac.jp

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Science 285, 1074-1077
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B. E. Nordin and P. Schimmel (1999)
J. Biol. Chem. 274, 6835-6838
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Proofreading by Isoleucyl-Transfer RNA Synthetase: Response.
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Science 283, 459a-459
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Proofreading by Isoleucyl-transfer RNA Synthetase.
X. Qiu (1998)
Science 282, 1955b-1955
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R. S. A. Lipman and Y.-M. Hou (1998)
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Activation of microhelix charging by localized helix destabilization.
R. W. Alexander, B. E. Nordin, and P. Schimmel (1998)
PNAS 95, 12214-12219
   Abstract »    Full Text »    PDF »
Species-specific Differences in Amino Acid Editing by Class II Prolyl-tRNA Synthetase.
P. J. Beuning and K. Musier-Forsyth (2001)
J. Biol. Chem. 276, 30779-30785
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Blocking site-to-site translocation of a misactivated amino acid by mutation of a class I tRNA synthetase.
A. C. Bishop, T. K. Nomanbhoy, and P. Schimmel (2002)
PNAS 99, 585-590
   Abstract »    Full Text »    PDF »
Misactivated amino acids translocate at similar rates across surface of a tRNA synthetase.
T. K. Nomanbhoy and P. R. Schimmel (2000)
PNAS 97, 5119-5122
   Abstract »    Full Text »    PDF »
A prokaryote and human tRNA synthetase provide an essential RNA splicing function in yeast mitochondria.
F. Houman, S. B. Rho, J. Zhang, X. Shen, C.-C. Wang, P. Schimmel, and S. A. Martinis (2000)
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   Abstract »    Full Text »    PDF »


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