Catalytic mechanism of the tryptophan activation reaction revealed by crystal structures of human tryptophanyl-tRNA synthetase in different enzymatic states

	Catalytic mechanism of the tryptophan activation reaction revealed by crystal structures of human tryptophanyl-tRNA synthetase in different enzymatic states
	Shen, N; Zhou, MY; Yang, B; Yu, YD; Dong, XC; Ding, JP
刊名	NUCLEIC ACIDS RESEARCH
	2008
卷号	36 期号:4 页码:1288-1299
通讯作者	Ding, JP (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,jpding@sibs.ac.cn
英文摘要	Human tryptophanyl-tRNA synthetase (hTrpRS) differs from its bacterial counterpart at several key positions of the catalytic active site and has an extra N-terminal domain, implying possibly a different catalytic mechanism. We report here the crystal structures of hTrpRS in complexes with Trp, tryptophanamide and ATP and tryptophanyl-AMP, respectively, which represent three different enzymatic states of the Trp activation reaction. Analyses of these structures reveal the molecular basis of the mechanisms of the substrate recognition and the activation reaction. The dimeric hTrpRS is structurally and functionally asymmetric with half-of-the-sites reactivity. Recognition of Trp is by an induced-fit mechanism involving conformational change of the AIDQ motif that creates a perfect pocket for the binding and activation of Trp and causes coupled movements of the N-terminal and C-terminal domains. The KMSAS loop appears to have an inherent flexibility and the binding of ATP stabilizes it in a closed conformation that secures the position of ATP for catalysis. Our structural data indicate that the catalytic mechanism of the Trp activation reaction by hTrpRS involves more moderate conformational changes of the structural elements at the active site to recognize and bind the substrates, which is more complex and fine-tuned than that of bacterial TrpRS.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	SITE-DIRECTED MUTAGENESIS ; AMINO-ACID ACTIVATION ; TRANSITION-STATE ; BEEF PANCREAS ; GENETIC-CODE ; BINDING-SITE ; ACTIVE-SITE ; AMINOACYLATION ; RECOGNITION ; ADENYLATE
收录类别	SCI
语种	英语
WOS记录号	WOS:000253857400028
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1369]
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	Shen, N,Zhou, MY,Yang, B,et al. Catalytic mechanism of the tryptophan activation reaction revealed by crystal structures of human tryptophanyl-tRNA synthetase in different enzymatic states[J]. NUCLEIC ACIDS RESEARCH,2008,36(4):1288-1299.
APA	Shen, N,Zhou, MY,Yang, B,Yu, YD,Dong, XC,&Ding, JP.(2008).Catalytic mechanism of the tryptophan activation reaction revealed by crystal structures of human tryptophanyl-tRNA synthetase in different enzymatic states.NUCLEIC ACIDS RESEARCH,36(4),1288-1299.
MLA	Shen, N,et al."Catalytic mechanism of the tryptophan activation reaction revealed by crystal structures of human tryptophanyl-tRNA synthetase in different enzymatic states".NUCLEIC ACIDS RESEARCH 36.4(2008):1288-1299.