Sieves in sequence
Fersht, A.R.
Science 280(5363): 541
1998
ISSN/ISBN: 0036-8075 PMID: 9575099 Document Number: 497519
In this issue, O. Nureki et al. resolve a classic problem in molecular recognition. In 1958, Linus Pauling observed that a protein must keep ligands that are smaller than the correct one out of its binding site. In modern terms, this refers to how the isoleucine-selective enzyme, isoleucyl-tRNA synthetase (IleRS), excludes valine, which is smaller than isoleucine by just one methylene group. Nureki et al. reveal in molecular detail the structure of the IleRS, demonstrating that it operates at high specificity by double-sieve editing. They uncovered this structure from Thermus thermophilus and its complexes with isoleucine and valine.