Crystal structures of Saccharomyces cerevisiae tryptophanyl-tRNA synthetase: new insights into the mechanism of tryptophan activation and implications for anti-fungal drug design | |
Zhou, MY; Dong, XC; Shen, N; Zhong, C; Ding, JP | |
刊名 | NUCLEIC ACIDS RESEARCH |
2010 | |
卷号 | 38期号:10页码:3399-3413 |
通讯作者 | Zhong, C (reprint author), Chinese Acad Sci, State Key Lab Mol Biol, Shanghai 200031, Peoples R China.,czhong@sibs.ac.cn ; jpding@sibs.ac.cn |
英文摘要 | 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. |
学科主题 | Biochemistry & Molecular Biology |
类目[WOS] | Biochemistry & Molecular Biology |
关键词[WOS] | AMINO-ACID ACTIVATION ; PARTICLE MESH EWALD ; TRANSITION-STATE ; MOLECULAR SIMULATIONS ; RECOGNITION ; BINDING ; TRPRS ; SITE ; ATP ; CRYSTALLOGRAPHY |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000278442600029 |
内容类型 | 期刊论文 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/1060] |
专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
推荐引用方式 GB/T 7714 | Zhou, MY,Dong, XC,Shen, N,et al. Crystal structures of Saccharomyces cerevisiae tryptophanyl-tRNA synthetase: new insights into the mechanism of tryptophan activation and implications for anti-fungal drug design[J]. NUCLEIC ACIDS RESEARCH,2010,38(10):3399-3413. |
APA | Zhou, MY,Dong, XC,Shen, N,Zhong, C,&Ding, JP.(2010).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 RESEARCH,38(10),3399-3413. |
MLA | Zhou, MY,et al."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 RESEARCH 38.10(2010):3399-3413. |
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