Crystal structures of Saccharomyces cerevisiae tryptophanyl-tRNA synthetase: new insights into the mechanism of tryptophan activation and implications for anti-fungal drug design.

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 mov

SUBMITTER: Zhou M 

PROVIDER: S-EPMC2879500 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature