2XGT
Asparaginyl-tRNA synthetase from Brugia malayi complexed with the sulphamoyl analogue of asparaginyl-adenylate
Summary for 2XGT
| Entry DOI | 10.2210/pdb2xgt/pdb |
| Related | 2XTI |
| Descriptor | ASPARAGINYL-TRNA SYNTHETASE, CYTOPLASMIC, GLYCEROL, 5'-O-[N-(L-ASPARAGINYL)SULFAMOYL]ADENOSINE, ... (5 entities in total) |
| Functional Keywords | ligase, atp-binding, protein biosynthesis |
| Biological source | BRUGIA MALAYI |
| Total number of polymer chains | 2 |
| Total formula weight | 101177.76 |
| Authors | Crepin, T.,Haertlein, M.,Kron, M.,Cusack, S. (deposition date: 2010-06-07, release date: 2010-12-15, Last modification date: 2024-05-01) |
| Primary citation | 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 Cited by 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: 21134380DOI: 10.1016/J.JMB.2010.11.049 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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