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

Research output: Contribution to journalArticlepeer-review

320 Citations (Scopus)


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 exits on a globular β-barrel domain that protrudes from the aminoacylation domain.

Original languageEnglish
Pages (from-to)578-582
Number of pages5
Issue number5363
Publication statusPublished - Apr 24 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General


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