3KT8

Crystal structure of S. cerevisiae tryptophanyl-tRNA synthetase in complex with L-tryptophanamide

Summary for 3KT8

• Entry DOI: 10.2210/pdb3kt8/pdb
• Related: 3KT0 3KT3 3KT6
• Descriptor: Tryptophanyl-tRNA synthetase, cytoplasmic, L-TRYPTOPHANAMIDE, SULFATE ION, ... (4 entities in total)
• Functional Keywords: tryptophanyl-trna synthetase, s. cerevisiae, sulfate ion, amino acid activation, catalytic mechanism, tryptophanamide, aminoacyl-trna synthetase, atp-binding, cytoplasm, ligase, nucleotide-binding, protein biosynthesis
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Cellular location: Cytoplasm: Q12109
• Total number of polymer chains: 4
• Total formula weight: 202765.97

Authors

Zhou, M.,Dong, X.,Zhong, C.,Shen, N.,Ding, J. (deposition date: 2009-11-24, release date: 2010-02-16, Last modification date: 2023-11-01)

Primary citation

Zhou, M.,Dong, X.,Shen, N.,Zhong, C.,Ding, J.
Crystal structures of Saccharomyces cerevisiae tryptophanyl-tRNA synthetase: new insights into the mechanism of tryptophan activation and implications for anti-fungal drug design
Nucleic Acids Res., 38:3399-3413, 2010

PubMed Abstract: Specific activation of amino acids by aminoacyl-tRNA synthetases is essential for maintaining translational fidelity. Here, we present crystal structures of Saccharomyces cerevisiae tryptophanyl-tRNA synthetase (sTrpRS) in apo form and in complexes with various ligands. In each complex, there is a sulfate ion bound at the active site which mimics the alpha- or beta-phosphate group of ATP during tryptophan activation. In particular, in one monomer of the sTrpRS-TrpNH(2)O complex, the sulfate ion appears to capture a snapshot of the alpha-phosphate of ATP during its movement towards tryptophan. Simulation study of a human TrpRS-Trp-ATP model shows that during the catalytic process the alpha-phosphate of ATP is driven to an intermediate position equivalent to that of the sulfate ion, then moves further and eventually fluctuates at around 2 A from the nucleophile. A conserved Arg may interact with the oxygen in the scissile bond at the transition state, indicating its critical role in the nucleophilic substitution. Taken together, eukaryotic TrpRSs may adopt an associative mechanism for tryptophan activation in contrast to a dissociative mechanism proposed for bacterial TrpRSs. In addition, structural analysis of the apo sTrpRS reveals a unique feature of fungal TrpRSs, which could be exploited in rational antifungal drug design.

PubMed: 20123733
DOI: 10.1093/nar/gkp1254

Experimental method

X-RAY DIFFRACTION (3 Å)