Structure, Function, and Inhibition of Staphylococcus aureus Heptaprenyl Diphosphate Synthase
文献类型：期刊论文
| 作者 | Desai, Janish1; Liu, Yi-Liang2; Wei, Hongli3; Liu, Weidong3; Ko, Tzu-Ping4; Guo, Rey-Ting3; Oldfield, Eric1,2 |
| 刊名 | CHEMMEDCHEM
 |
| 出版日期 | 2016-09-06 |
| 卷号 | 11期号:17页码:1915-1923 |
| 关键词 | bisphosphonates heptaprenyl diphosphate synthase menaquinone biosynthesis Staphylococcus aureus substrate-induced inhibition |
| 英文摘要 | We report the first structure of heptaprenyl diphosphate synthase from Staphylococcus aureus (SaHepPPS), together with an investigation of its mechanism of action and inhibition. The protein is involved in the formation of menaquinone, a key electron transporter in many bacteria, including pathogens. SaHepPPS consists of a catalytic subunit (SaHepPPS-2) having two DDXXD motifs and a regulatory subunit (SaHepPPS-1) that lacks these motifs. High concentrations of the substrates, isopentenyl diphosphate and farnesyl diphosphate, inhibit the enzyme, which is also potently inhibited by bisphosphonates. The most active inhibitors (K-i approximate to 200nm) were N-alkyl analogues of zoledronate containing approximate to C-6 alkyl side chains. They were modestly active against S.aureus cell growth, and growth inhibition was partially rescued by the addition of menaquinone-7. Because SaHepPPS is essential for S.aureus cell growth, its structure is of interest in the context of the development of menaquinone biosynthesis inhibitors as potential antibiotic leads. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 类目[WOS] | Chemistry, Medicinal ; Pharmacology & Pharmacy |
| 研究领域[WOS] | Pharmacology & Pharmacy |
| 关键词[WOS] | TARGETING ISOPRENOID BIOSYNTHESIS ; DRUG DISCOVERY ; X-RAY ; BISPHOSPHONATES ; MENAQUINONE ; REFINEMENT ; ALIGNMENT ; SEQUENCE ; BEDSIDE ; SYSTEM |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000383610100006 |
| 源URL | [http://124.16.173.210/handle/834782/2925]  |
| 专题 | 天津工业生物技术研究所_结构生物学与蛋白酶学实验室 郭瑞庭_期刊论文 |
| 作者单位 | 1.Univ Illinois, Ctr Biophys & Quantitat Biol, 1110 West Green St, Urbana, IL 61801 USA 2.Univ Illinois, Dept Chem, 600 South Matthews Ave, Urbana, IL 61801 USA 3.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Ind Enzymes Natl Engn Lab, Tianjin 300308, Peoples R China 4.Acad Sinica, Inst Biol Chem, 128 Acad Rd, Taipei 11529, Taiwan |
| 推荐引用方式 GB/T 7714 | Desai, Janish,Liu, Yi-Liang,Wei, Hongli,et al. Structure, Function, and Inhibition of Staphylococcus aureus Heptaprenyl Diphosphate Synthase[J]. CHEMMEDCHEM,2016,11(17):1915-1923. |
| APA | Desai, Janish.,Liu, Yi-Liang.,Wei, Hongli.,Liu, Weidong.,Ko, Tzu-Ping.,...&Oldfield, Eric.(2016).Structure, Function, and Inhibition of Staphylococcus aureus Heptaprenyl Diphosphate Synthase.CHEMMEDCHEM,11(17),1915-1923. |
| MLA | Desai, Janish,et al."Structure, Function, and Inhibition of Staphylococcus aureus Heptaprenyl Diphosphate Synthase".CHEMMEDCHEM 11.17(2016):1915-1923. |
入库方式： OAI收割
来源：天津工业生物技术研究所
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