The catalytic intermediate stabilized by a "Down" active site loop for diaminopimelate decarboxylase from Helicobacter pylori - Enzymatic characterization with crystal structure analysis

	The catalytic intermediate stabilized by a "Down" active site loop for diaminopimelate decarboxylase from Helicobacter pylori - Enzymatic characterization with crystal structure analysis
	Hu, TC; Wu, DL; Chen, J; Ding, JP; Jiang, HL; Shen, X
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2008
卷号	283 期号:30 页码:21284-21293
通讯作者	Jiang, HL (reprint author), Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China.,hljiang@mail.shcnc.ac.cn ; xshen@mail.shcnc.ac.cn
英文摘要	The meso-diaminopimelate decarboxylase (DAPDC, EC 4.1.1.20) catalyzes the final step of L-lysine biosynthesis in bacteria and is regarded as a target for the discovery of antibiotics. Here we report the 2.3 angstrom crystal structure of DAPDC from Helicobacter pylori (HpDAPDC). The structure, in which the product L-lysine forms a Schiff base with the cofactor pyridoxal 5'-phosphate, provides structural insight into the substrate specificity and catalytic mechanism of the enzyme, and implies that the carboxyl to be cleaved locates at the si face of the cofactor. To our knowledge, this might be the first reported external aldimine of DAPDC. Moreover, the active site loop of HpDAPDC is in a "down" conformation and shields the ligand from solvent. Mutations of Ile(148) from the loop greatly impaired the catalytic efficiency. Combining the structural analysis of the I148L mutant, we hypothesize that HpDAPDC adopts an induced-fit catalytic mechanism in which this loop cycles through "down" and "up" conformations to stabilize intermediates and release product, respectively. Our work is expected to provide clues for designing specific inhibitors of DAPDC.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	AMINO-ACID DECARBOXYLASES ; X-RAY-STRUCTURE ; BRUCEI ORNITHINE-DECARBOXYLASE ; PYRIDOXAL-PHOSPHATE ENZYMES ; TRYPANOSOMA-BRUCEI ; ALANINE RACEMASE ; ANTIBIOTIC-RESISTANCE ; SUBSTRATE-SPECIFICITY ; BIOSYNTHESIS ; CARBOXYLATE
收录类别	SCI
语种	英语
WOS记录号	WOS:000257746100070
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1476]
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	Hu, TC,Wu, DL,Chen, J,et al. The catalytic intermediate stabilized by a "Down" active site loop for diaminopimelate decarboxylase from Helicobacter pylori - Enzymatic characterization with crystal structure analysis[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2008,283(30):21284-21293.
APA	Hu, TC,Wu, DL,Chen, J,Ding, JP,Jiang, HL,&Shen, X.(2008).The catalytic intermediate stabilized by a "Down" active site loop for diaminopimelate decarboxylase from Helicobacter pylori - Enzymatic characterization with crystal structure analysis.JOURNAL OF BIOLOGICAL CHEMISTRY,283(30),21284-21293.
MLA	Hu, TC,et al."The catalytic intermediate stabilized by a "Down" active site loop for diaminopimelate decarboxylase from Helicobacter pylori - Enzymatic characterization with crystal structure analysis".JOURNAL OF BIOLOGICAL CHEMISTRY 283.30(2008):21284-21293.