X-ray crystallographic and enzymatic analyses of shikimate dehydrogenase from Staphylococcus epidermidis
文献类型：期刊论文
| 作者 | Han, Cong5,6; Hu, Tiancen3; Wu, Dalei3; Qu, Su5,6; Zhou, Jiahai4; Ding, Jianping1,2; Shen, Xu3 ; Qu, Di5,6; Jiang, Hualiang3
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| 刊名 | FEBS JOURNAL
 |
| 出版日期 | 2009-02 |
| 卷号 | 276期号:4页码:1125-1139 |
| 关键词 | crystal structure shikimate dehydrogenase shikimate pathway site-directed mutagenesis Staphylococcus epidermidis |
| ISSN号 | 1742-464X |
| DOI | 10.1111/j.1742-4658.2008.06856.x |
| 文献子类 | Article |
| 英文摘要 | Shikimate dehydrogenase (SDH) catalyzes the NADPH-dependent reduction of 3-dehydroshikimate to shikimate in the shikimate pathway. In this study, we determined the kinetic properties and crystal structures of Staphylococcus epidermidis SDH (SeSDH) both in its ligand-free form and in complex with shikimate. SeSDH has a k(cat) of 22.8 s(-1) and a K-m of 73 mu m towards shikimate, and a K-m of 100 mu m towards NADP. The overall folding of SeSDH comprises the N-terminal alpha/beta domain for substrate binding and the C-terminal Rossmann fold for NADP binding. The active site is within a large groove between the two domains. Residue Tyr211, normally regarded as important for substrate binding, does not interact with shikimate in the binary SeSDH-shikimate complex structure. However, the Y211F mutation leads to a significant decrease in k(cat) and a minor increase in the K-m for shikimate. The results indicate that the main function of Tyr211 may be to stabilize the catalytic intermediate during catalysis. The NADP-binding domain of SeSDH is less conserved. The usually long helix specifically recognizing the adenine ribose phosphate is substituted with a short 3(10) helix in the NADP-binding domain. Moreover, the interdomain angle of SeSDH is the widest among all known SDH structures, indicating an inactive 'open' state of the SeSDH structure. Thus, a 'closing' process might occur upon NADP binding to bring the cofactor close to the substrate for catalysis. |
| WOS关键词 | AMINO-ACID BIOSYNTHESIS ; CRYSTAL-STRUCTURE ; MYCOBACTERIUM-TUBERCULOSIS ; 5-DEHYDROGENASE ; PATHWAY ; AROE ; INSIGHTS ; INFECTIONS ; MECHANISM ; DENSITY |
| 资助项目 | State Key Program of Basic Research of China[2002CB512803] ; International Science and Technology Cooperation Program of China[2006DFA32760] ; National Natural Science Foundation of China[30800036] ; China Postdoctoral Science Foundation[200801172] ; China Postdoctoral Science Foundation[20060400574] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000262666900021 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279332]  |
| 专题 | 药理学第三研究室 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 药物发现与设计中心 |
| 通讯作者 | Qu, Di |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Beijing 100864, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Res Ctr Struct Biol, Beijing 100864, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Beijing 100864, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Organ Chem, Beijing 100864, Peoples R China; 5.Fudan Univ, Shanghai Med Coll, Inst Med Microbiol, Inst Biomed Sci, Shanghai 200032, Peoples R China; 6.Fudan Univ, Shanghai Med Coll, Inst Med Microbiol, Key Lab Med Mol Virol, Shanghai 200032, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Han, Cong,Hu, Tiancen,Wu, Dalei,et al. X-ray crystallographic and enzymatic analyses of shikimate dehydrogenase from Staphylococcus epidermidis[J]. FEBS JOURNAL,2009,276(4):1125-1139. |
| APA | Han, Cong.,Hu, Tiancen.,Wu, Dalei.,Qu, Su.,Zhou, Jiahai.,...&Jiang, Hualiang.(2009).X-ray crystallographic and enzymatic analyses of shikimate dehydrogenase from Staphylococcus epidermidis.FEBS JOURNAL,276(4),1125-1139. |
| MLA | Han, Cong,et al."X-ray crystallographic and enzymatic analyses of shikimate dehydrogenase from Staphylococcus epidermidis".FEBS JOURNAL 276.4(2009):1125-1139. |
入库方式： OAI收割
来源：上海药物研究所
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