Premium
Idiosyncrasy and identity in the prokaryotic phe‐system: Crystal structure of E. coli phenylalanyl‐tRNA synthetase complexed with phenylalanine and AMP
Author(s) -
Mermershtain Inbal,
Finarov Igal,
Klipcan Liron,
Kessler Naama,
Rozenberg Haim,
Safro Mark G.
Publication year - 2011
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.549
Subject(s) - transfer rna , stereochemistry , protein subunit , phenylalanine , heterotetramer , aminoacyl trna synthetase , helix (gastropod) , c terminus , protein structure , biology , chemistry , biochemistry , amino acid , rna , gene , ecology , snail
The crystal structure of Phenylalanyl‐tRNA synthetase from E. coli ( Ec PheRS), a class II aminoacyl‐tRNA synthetase, complexed with phenylalanine and AMP was determined at 3.05 Å resolution. Ec PheRS is a (αβ) 2 heterotetramer: the αβ heterodimer of Ec PheRS consists of 11 structural domains. Three of them: the N‐terminus, A1 and A2 belong to the α‐subunit and B1‐B8 domains to the β subunit. The structure of Ec PheRS revealed that architecture of four helix‐bundle interface, characteristic of class IIc heterotetrameric aaRSs, is changed: each of the two long helices belonging to CLM transformed into the coil‐short helix structural fragments. The N‐terminal domain of the α‐subunit in Ec PheRS forms compact triple helix domain. This observation is contradictory to the structure of the apo form of Tt PheRS, where N‐terminal domain was not detected in the electron density map. Comparison of Ec PheRS structure with Tt PheRS has uncovered significant rearrangements of the structural domains involved in tRNA Phe binding/translocation. As it follows from modeling experiments, to achieve a tighter fit with anticodon loop of tRNA, a shift of ∼5 Å is required for C‐terminal domain B8, and of ∼6 to 7 Å for the whole N terminus. Ec PheRSs have emerged as an important target for the incorporation of novel amino acids into genetic code. Further progress in design of novel compounds is anticipated based on the structural data of Ec PheRS.