1O5T

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

1O5T の概要

• エントリーDOI: 10.2210/pdb1o5t/pdb
• 分子名称: Tryptophanyl-tRNA synthetase (2 entities in total)
• 機能のキーワード: rossmann fold, four helix bundle, ligase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P23381
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43386.48

構造登録者

Yu, Y.,Liu, Y.,Shen, N.,Xu, X.,Jia, J.,Jin, Y.,Arnold, E.,Ding, J. (登録日: 2003-10-05, 公開日: 2004-07-06, 最終更新日: 2023-12-27)

主引用文献

Yu, Y.,Liu, Y.,Shen, N.,Xu, X.,Xu, F.,Jia, J.,Jin, Y.,Arnold, E.,Ding, J.
Crystal Structure of Human Tryptophanyl-tRNA Synthetase Catalytic Fragment
J.BIOL.CHEM., 279:8378-8388, 2004

PubMed Abstract: 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.

PubMed: 14660560
DOI: 10.1074/jbc.M311284200

実験手法

X-RAY DIFFRACTION (2.5 Å)