1o5t

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models 1o5t, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of the aminoacylation catalytic fragment of human tryptophanyl-tRNA synthetase

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Human tryptophanyl-tRNA synthetase (hTrpRS) produces a full-length and, three N terminus-truncated forms through alternative splicing and, proteolysis. The shortest fragment that contains the aminoacylation, catalytic fragment (T2-hTrpRS) exhibits the most potent angiostatic, activity. We report here the crystal structure of T2-hTrpRS at 2.5 A, resolution, which was solved using the multi-wavelength anomalous, diffraction method. T2-hTrpRS shares a very low sequence homology of 22%, with Bacillus stearothermophilus TrpRS (bTrpRS); however, their overall, structures are strikingly similar. Structural comparison of T2-hTrpRS with, bTrpRS reveals substantial structural differences in the substrate-binding, pocket and at the entrance to the pocket that play important roles in, substrate binding and tRNA binding. T2-hTrpRS has a wide opening to the, active site and adopts a compact conformation similar to the closed, conformation of bTrpRS. These results suggest that mammalian and bacterial, TrpRSs might use different mechanisms to recognize the substrate. Modeling, studies indicate that tRNA binds with the dimeric enzyme and interacts, primarily with the connective polypeptide 1 of hTrpRS via its acceptor arm, and the alpha-helical domain of hTrpRS via its anticodon loop. Our results, also suggest that the angiostatic activity is likely located at the, alpha-helical domain, which resembles the short chain cytokines.

Disease

Known disease associated with this structure: Wolcott-Rallison syndrome OMIM:[604032]

About this Structure

1O5T is a Single protein structure of sequence from Homo sapiens. Active as Tryptophan--tRNA ligase, with EC number 6.1.1.2 Full crystallographic information is available from OCA.

Reference

Crystal structure of human tryptophanyl-tRNA synthetase catalytic fragment: insights into substrate recognition, tRNA binding, and angiogenesis activity., Yu Y, Liu Y, Shen N, Xu X, Xu F, Jia J, Jin Y, Arnold E, Ding J, J Biol Chem. 2004 Feb 27;279(9):8378-88. Epub 2003 Dec 5. PMID:14660560

Page seeded by OCA on Fri Feb 15 16:33:11 2008