Structural basis of specificity of a peptidyl urokinase inhibitor, upain-1
文献类型：期刊论文
| 作者 | G. X. Zhao ; C. Yuan ; T. Wind ; Z. X. Huang ; P. A. ; reasen ; M. D. Huang |
| 刊名 | Journal of Structural Biology
 |
| 出版日期 | 2007-10 |
| 卷号 | 160期号:1页码:1-10 |
| 关键词 | urokinase-type plasminogen activator peptidyl inhibitor crystal structure pharmacophore activator pro-upa plasminogen-activator crystal-structure single-chain selective inhibitors drug design complex receptor system domain |
| ISSN号 | 1047-8477 |
| 中文摘要 | Urokinase-type plasminogen activator (uPA) plays a crucial role in the regulation of plasminogen activation, tumor cell adhesion and migration. The inhibition of uPA activity is a promising mechanism for anti-cancer therapy. A cyclic peptidyl inhibitor, upain-1, CSWRGLENHRMC, was identified recently as a competitive and highly specific uPA inhibitor. We determined the crystal structure of uPA in complex with upain-1 at 2.15 angstrom. The structure reveals that the cyclic peptide adopts a rigid conformation stabilized by a disulfide bond (residues 1-12) and three tight beta turns (residues 3-6, 6-9, 9-12). The Glu7 residue of upain-1 forms hydrogen bonds with the main chain nitrogen atoms of residues 4, 5, and 6 of upain-1, and is also critical for maintaining the active conformation of upain-1. The Arg4 of upain-1 is inserted into the uPA's specific S1 pocket. The Ser2 residue of upain-1 locates close to the S I P pocket of uPA. The Gly5 and Glu7 residues of upain-1 occupy the S2 pocket and the oxyanion hole of uPA, respectively. Furthermore, the Asn8 residue of upain-1 binds to the 37- and 60-loops of uPA and renders the specificity of upain-1 for uPA. Based on this structure, a new pharmacophore for the design of highly specific uPA inhibitors was proposed. (c) 2007 Elsevier Inc. All rights reserved. |
| 语种 | 英语 |
| 公开日期 | 2013-04-01 |
| 源URL | [http://ir.fjirsm.ac.cn/handle/350002/6902]  |
| 专题 | 福建物质结构研究所_中科院福建物质结构研究所_期刊论文 |
| 推荐引用方式 GB/T 7714 | G. X. Zhao,C. Yuan,T. Wind,et al. Structural basis of specificity of a peptidyl urokinase inhibitor, upain-1[J]. Journal of Structural Biology,2007,160(1):1-10. |
| APA | G. X. Zhao.,C. Yuan.,T. Wind.,Z. X. Huang.,P. A..,...&M. D. Huang.(2007).Structural basis of specificity of a peptidyl urokinase inhibitor, upain-1.Journal of Structural Biology,160(1),1-10. |
| MLA | G. X. Zhao,et al."Structural basis of specificity of a peptidyl urokinase inhibitor, upain-1".Journal of Structural Biology 160.1(2007):1-10. |
入库方式： OAI收割
来源：福建物质结构研究所
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