Rational redesign of inhibitors of furin/kexin processing proteases by electrostatic mutations
文献类型：期刊论文
| 作者 | Cai, XH; Zhang, Q; Ding, DF |
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2004 |
| 卷号 | 25期号:12页码:1712-1718 |
| 关键词 | furin kexin eglin c drug design electrostatic mutation |
| 通讯作者 | Ding, DF (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Grad Sch, Inst Biochem & Cell Biol,Key Lab Prote, Shanghai 200031, Peoples R China.,dingdafu@server.shcnc.ac.cn |
| 英文摘要 | AIM: To model the three-dimensional structure and investigate the interaction mechanism of the proprotein convertase furin/kexin and their inhibitors (eglin c mutants). METHODS: The three-dimensional complex structures of furin/kexin with its inhibitors, eglin c mutants, were generated by modeller program using the newly published X-ray crystallographical structures of mouse furin and yeast kexin as templates. The electrostatic interaction energy of each complex was calculated and the results were compared with the experimentally determined inhibition constants to find the correlation between them. RESULTS: High quality models of furin/kexin-eglin c mutants were obtained and used for calculation of the electrostatic interaction energies between the proteases and their inhibitors. The calculated electrostatic energies of interaction showed a linear correlation to the experimental inhibition constants. CONCLUSION: The modeled structures give good explanations of the specificity of eglin c mutants to furin/kexin. The electrostatic interactions play important roles in inhibitory activity of eglin c mutants to furin/kexin. The results presented here provided quantitative structural and functional information concerning the role of the charge-charge interactions in the binding of furin/kexin and their inhibitors. |
| 学科主题 | Chemistry ; Pharmacology & Pharmacy |
| 类目[WOS] | Chemistry, Multidisciplinary ; Pharmacology & Pharmacy |
| 关键词[WOS] | SITE-DIRECTED MUTAGENESIS ; EGLIN-C MUTANTS ; CRYSTAL-STRUCTURE ; FURIN ; DESIGN ; SPECIFICITY ; COMPLEX ; ENZYME ; KEXIN |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000225845200022 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/2159]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Cai, XH,Zhang, Q,Ding, DF. Rational redesign of inhibitors of furin/kexin processing proteases by electrostatic mutations[J]. ACTA PHARMACOLOGICA SINICA,2004,25(12):1712-1718. |
| APA | Cai, XH,Zhang, Q,&Ding, DF.(2004).Rational redesign of inhibitors of furin/kexin processing proteases by electrostatic mutations.ACTA PHARMACOLOGICA SINICA,25(12),1712-1718. |
| MLA | Cai, XH,et al."Rational redesign of inhibitors of furin/kexin processing proteases by electrostatic mutations".ACTA PHARMACOLOGICA SINICA 25.12(2004):1712-1718. |
入库方式： OAI收割
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。