Enzyme Structure with Two Catalytic Sites for Double-Sieve Selection of Substrate
- 24 April 1998
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 280 (5363), 578-582
- https://doi.org/10.1126/science.280.5363.578
Abstract
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 β-barrel domain that protrudes from the aminoacylation domain.Keywords
This publication has 18 references indexed in Scilit:
- Discrete Determinants in Transfer RNA for Editing and AminoacylationScience, 1997
- [20] Processing of X-ray diffraction data collected in oscillation modeMethods in Enzymology, 1997
- Aminoacylation error correctionNature, 1996
- Contribution of Hydrophobic Residues to the Stability of Human Lysozyme: Calorimetric Studies and X-ray Structural Analysis of the Five Isoleucine to Valine MutantsJournal of Molecular Biology, 1995
- NMRPipe: A multidimensional spectral processing system based on UNIX pipesJournal of Biomolecular NMR, 1995
- The CCP4 suite: programs for protein crystallographyActa crystallographica. Section D, Structural biology, 1994
- Mutational Isolation of a Sieve for Editing in a Transfer RNA SynthetaseScience, 1994
- A left‐handed crossover involved in amidohydrolase catalysisFEBS Letters, 1993
- Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifsNature, 1990
- Isoleucyl-tRNA synthetase from bakers' yeast: multistep proofreading in discrimination between isoleucine and valine with modulated accuracy, a scheme for molecular recognition by energy dissipationBiochemistry, 1985