1R6U

Crystal structure of an active fragment of human tryptophanyl-tRNA synthetase with cytokine activity

Summary for 1R6U

• Entry DOI: 10.2210/pdb1r6u/pdb
• Related: 1N3L 1NTG 1R6T
• Descriptor: Tryptophanyl-tRNA synthetase, TRYPTOPHANYL-5'AMP, GLYCEROL, ... (4 entities in total)
• Functional Keywords: class ic trna synthetase, rossmann fold catalytic domain, anticodon recognition domain, bound trp-amp, ligase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P23381
• Total number of polymer chains: 2
• Total formula weight: 101033.81

Authors

Yang, X.-L.,Otero, F.J.,Skene, R.J.,McRee, D.E.,Ribas de Pouplana, L.,Schimmel, P. (deposition date: 2003-10-16, release date: 2004-01-06, Last modification date: 2024-10-30)

Primary citation

Yang, X.-L.,Guo, M.,Kapoor, M.,Ewalt, K.L.,Otero, F.J.,Skene, R.J.,McRee, D.E.,Schimmel, P.
Functional and crystal structure analysis of active site adaptations of a potent anti-angiogenic human tRNA synthetase
Structure, 15:793-805, 2007

PubMed Abstract: Higher eukaryote tRNA synthetases have expanded functions that come from enlarged, more differentiated structures that were adapted to fit aminoacylation function. How those adaptations affect catalytic mechanisms is not known. Presented here is the structure of a catalytically active natural splice variant of human tryptophanyl-tRNA synthetase (TrpRS) that is a potent angiostatic factor. This and related structures suggest that a eukaryote-specific N-terminal extension of the core enzyme changed substrate recognition by forming an active site cap. At the junction of the extension and core catalytic unit, an arginine is recruited to replace a missing landmark lysine almost 200 residues away. Mutagenesis, rapid kinetic, and substrate binding studies support the functional significance of the cap and arginine recruitment. Thus, the enzyme function of human TrpRS has switched more to the N terminus of the sequence. This switch has the effect of creating selective pressure to retain the N-terminal extension for functional expansion.

PubMed: 17637340
DOI: 10.1016/j.str.2007.05.009

Experimental method

X-RAY DIFFRACTION (2 Å)