2XTI

Asparaginyl-tRNA synthetase from Brugia malayi complexed with ATP:Mg and L-Asp-beta-NOH adenylate:PPi:Mg

2XTI の概要

• エントリーDOI: 10.2210/pdb2xti/pdb
• 関連するPDBエントリー: 2XGT
• 分子名称: ASPARAGINYL-TRNA SYNTHETASE\, CYTOPLASMIC\, PUTATIVE, 5'-O-[(R)-{[(2S)-2-amino-4-(hydroxyamino)-4-oxobutanoyl]oxy}(hydroxy)phosphoryl]adenosine, PYROPHOSPHATE 2-, ... (6 entities in total)
• 機能のキーワード: ligase, atp-binding, protein biosynthesis, filariasis
• 由来する生物種: BRUGIA MALAYI (FILARIAL NEMATODE WORM)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 101738.90

構造登録者

Crepin, T.,Haertlein, M.,Kron, M.,Cusack, S. (登録日: 2010-10-10, 公開日: 2010-12-15, 最終更新日: 2023-12-20)

主引用文献

Crepin, T.,Peterson, F.,Haertlein, M.,Jensen, D.,Wang, C.,Cusack, S.,Kron, M.
A Hybrid Structural Model of the Complete Brugia Malayi Cytoplasmic Asparaginyl-tRNA Synthetase.
J.Mol.Biol., 405:1056-, 2011

PubMed Abstract: Aminoacyl-tRNA synthetases are validated molecular targets for anti-infective drug discovery because of their essentiality in protein synthesis. Thanks to genome sequencing, it is now possible to systematically study aminoacyl-tRNA synthetases from human eukaryotic parasites as putative targets for novel drug discovery. As part of a program targeting class IIb asparaginyl-tRNA synthetases (AsnRS) from the parasitic nematode Brugia malayi for anti-filarial drugs, we report the complete structure of a eukaryotic AsnRS. Metazoan and fungal AsnRS differ from their bacterial homologues by the addition of a conserved N-terminal extension of about 110 residues whose structure we have determined by solution NMR for the B. malayi enzyme. In addition, we solved by X-ray crystallography a series of structures of the catalytically active N-terminally truncated enzyme (residues 112-548), allowing the structural basis for the mechanism of asparagine activation to be elucidated. The N-terminal domain contains a structured region with a novel fold featuring a lysine-rich helix that is shown by NMR to interact with tRNA. This is connected by an unstructured tether to the remainder of the enzyme, which is highly similar to the known structure of bacterial AsnRS. These data enable a model of the complete AsnRS-tRNA complex to be constructed.

PubMed: 21134380
DOI: 10.1016/J.JMB.2010.11.049

実験手法

X-RAY DIFFRACTION (2.4 Å)