Inhibition of monometalated methionine aminopeptidase: Inhibitor discovery and crystallographic analysis
文献类型：期刊论文
| 作者 | Huang, Min ; Xie, Sheng-Xue; Ma, Ze-Qiang; Huang, Qing-Qing; Nan, Fa-Jun; Ye, Qi-Zhuang
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2007-11-15 |
| 卷号 | 50期号:23页码:5735-5742 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/jm700930k |
| 文献子类 | Article |
| 英文摘要 | Two divalent metal ions are commonly seen in the active-site cavity of methionine aminopeptidase, and at least one of the metal ions is directly involved in catalysis. Although ample structural and functional information is available for dimetalated enzyme, methionine aminopeptidase likely functions as a monometalated enzyme under physiological conditions. Information on structure, as well as catalysis and inhibition, of the monometalated enzyme is lacking. By improving conditions of high-throughput screening, we identified a unique inhibitor with specificity toward the monometalated enzyme. Kinetic characterization indicates a mutual exclusivity in binding between the inhibitor and the second metal ion at the active site. This is confirmed by X-ray structure, and this inhibitor coordinates with the first metal ion and occupies the space normally occupied by the second metal ion. Kinetic and structural analyses of the inhibition by this and other inhibitors provide insight in designing effective inhibitors of methionine aminopeptidase. |
| WOS关键词 | METALLOFORM-SELECTIVE INHIBITION ; METAL-BINDING PROPERTIES ; ESCHERICHIA-COLI ; PYROCOCCUS-FURIOSUS ; STRUCTURAL-ANALYSIS ; OVALICIN ; ANGIOGENESIS ; IDENTIFICATION ; FUMAGILLIN ; TNP-470 |
| 资助项目 | NCRR NIH HHS[P20 RR015563-076478] ; NCRR NIH HHS[P20 RR015563-050012] ; NCRR NIH HHS[P20 RR016475] ; NCRR NIH HHS[P20 RR015563-059001] ; NCRR NIH HHS[P20 RR015563-060012] ; NCRR NIH HHS[P20 RR015563-069001] ; NCRR NIH HHS[P20 RR015563] ; NCRR NIH HHS[P20 RR017708] ; NIAID NIH HHS[R01 AI065898-04] ; NIAID NIH HHS[R01 AI065898-03] ; NIAID NIH HHS[R01 AI065898-02] ; NIAID NIH HHS[R01 AI065898-01] ; NIAID NIH HHS[R01 AI065898-05] ; NIAID NIH HHS[R01 AI065898] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000250809300027 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273113]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Ye, Qi-Zhuang |
| 作者单位 | 1.Univ Kansas, High Throughput Screening Lab, Lawrence, KS 66045 USA 2.Chinese Acad Sci, Shanghai Inst Mat Med, Chinese Natl Ctr Drug Screening, Shanghai 201203, Peoples R China 3.Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA |
| 推荐引用方式 GB/T 7714 | Huang, Min,Xie, Sheng-Xue,Ma, Ze-Qiang,et al. Inhibition of monometalated methionine aminopeptidase: Inhibitor discovery and crystallographic analysis[J]. JOURNAL OF MEDICINAL CHEMISTRY,2007,50(23):5735-5742. |
| APA | Huang, Min,Xie, Sheng-Xue,Ma, Ze-Qiang,Huang, Qing-Qing,Nan, Fa-Jun,&Ye, Qi-Zhuang.(2007).Inhibition of monometalated methionine aminopeptidase: Inhibitor discovery and crystallographic analysis.JOURNAL OF MEDICINAL CHEMISTRY,50(23),5735-5742. |
| MLA | Huang, Min,et al."Inhibition of monometalated methionine aminopeptidase: Inhibitor discovery and crystallographic analysis".JOURNAL OF MEDICINAL CHEMISTRY 50.23(2007):5735-5742. |
入库方式： OAI收割
来源：上海药物研究所
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