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

Content Provider	PubMed Central
Author	Zhou, Minyun Dong, Xianchi Shen, Ning Zhong, Chen Ding, Jianping
Copyright Year	2010
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 α- or β-phosphate group of ATP during tryptophan activation. In particular, in one monomer of the sTrpRS–TrpNH2O complex, the sulfate ion appears to capture a snapshot of the α-phosphate of ATP during its movement towards tryptophan. Simulation study of a human TrpRS–Trp–ATP model shows that during the catalytic process the α-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 Å 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.
Related Links	http://dx.doi.org/10.1093/nar/gkp1254
Ending Page	3413
Page Count	15
Starting Page	3399
File Format	PDF
ISSN	03051048
e-ISSN	13624962
Journal	Nucleic Acids Research
Issue Number	10
Volume Number	38
Language	English
Publisher	Oxford University Press
Publisher Date	2010-06-01
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics

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

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

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