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

文献类型：期刊论文

作者Hu, Tiancen1; Wu, Dalei1; Chen, Jing1; Ding, Jianping2; Jiang, Hualiang1; Shen, Xu1
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
出版日期2008-07-25
卷号283期号:30页码:21284-21293
ISSN号0021-9258
DOI10.1074/jbc.M801823200
文献子类Article
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.
WOS关键词AMINO-ACID DECARBOXYLASES ; X-RAY-STRUCTURE ; BRUCEI ORNITHINE-DECARBOXYLASE ; PYRIDOXAL-PHOSPHATE ENZYMES ; TRYPANOSOMA-BRUCEI ; ALANINE RACEMASE ; ANTIBIOTIC-RESISTANCE ; SUBSTRATE-SPECIFICITY ; BIOSYNTHESIS ; CARBOXYLATE
WOS研究方向Biochemistry & Molecular Biology
语种英语
WOS记录号WOS:000257746100070
出版者AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
源URL[http://119.78.100.183/handle/2S10ELR8/272861]  
专题药物发现与设计中心
中科院受体结构与功能重点实验室
新药研究国家重点实验室
药物化学研究室
药理学第三研究室
通讯作者Jiang, Hualiang
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 20031, Peoples R China
推荐引用方式
GB/T 7714		 Hu, Tiancen,Wu, Dalei,Chen, Jing,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, Tiancen,Wu, Dalei,Chen, Jing,Ding, Jianping,Jiang, Hualiang,&Shen, Xu.(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, Tiancen,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.

入库方式： OAI收割

来源：上海药物研究所

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