1wnz

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models 1wnz, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Isoleucyl-tRNA synthetase editing domain complexed with the post-transfer editing substrate analogue, Val-2AA

Overview

In isoleucyl-tRNA synthetase (IleRS), the "editing" domain contributes to, accurate aminoacylation by hydrolyzing the mis-synthesized intermediate, valyl-adenylate, in the "pre-transfer" editing mode and the incorrect, final product, valyl-tRNA(Ile), in the "post-transfer" editing mode. In, the present study, we determined the crystal structures of the Thermus, thermophilus IleRS editing domain complexed with the substrate analogues, in the pre and post-transfer modes, both at 1.7 A resolution. The active, site accommodates the two analogues differently, with the valine, side-chain rotated by about 120 degrees and the adenosine moiety oriented, upside down. The substrate-binding pocket adjusts to the, adenosine-monophosphate and adenosine moieties in the pre and, post-transfer modes, respectively, by flipping the Trp227 side-chain by, about 180 degrees . The substrate recognition mechanisms of IleRS are, characterized by the active-site rearrangement between the two editing, modes, and therefore differ from those of the homologous valyl and, leucyl-tRNA synthetases from T.thermophilus, in which the post-transfer, mode is predominant. Both modes of editing activities were reduced by, replacements of Trp227 with Ala, Val, Leu, and His, but not by those with, Phe and Tyr, indicating that the aromatic ring of Trp227 is important for, the substrate recognition. In both editing modes, Thr233 and His319, recognize the substrate valine side-chain, regardless of the valine, side-chain rotation, and reject the isoleucine side-chain. The T233A and, H319A mutants have detectable editing activities against the cognate, isoleucine.

About this Structure

1WNZ is a Single protein structure of sequence from Thermus thermophilus with 2VA as ligand. Active as Isoleucine--tRNA ligase, with EC number 6.1.1.5 Full crystallographic information is available from OCA.

Reference

Structural basis for substrate recognition by the editing domain of isoleucyl-tRNA synthetase., Fukunaga R, Yokoyama S, J Mol Biol. 2006 Jun 16;359(4):901-12. Epub 2006 Apr 25. PMID:16697013

Page seeded by OCA on Wed Nov 21 05:33:23 2007