中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 国家新药筛选中心
Structural analysis of inhibition of E-coli methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes

文献类型：期刊论文

作者Ma, Ze-Qiang1; Xie, Sheng-Xue1; Huang, Qing-Qing2; Nan, Fa-Jun2; Hurley, Thomas D.3; Ye, Qi-Zhuang1,3
刊名BMC STRUCTURAL BIOLOGY
出版日期2007-12-19
卷号7
ISSN号1472-6807
DOI10.1186/1472-6807-7-84
文献子类Article
英文摘要Background: Methionine aminopeptidase is a potential target of future antibacterial and anticancer drugs. Structural analysis of complexes of the enzyme with its inhibitors provides valuable information for structure-based drug design efforts. Results: Five new X-ray structures of such enzyme-inhibitor complexes were obtained. Analysis of these and other three similar structures reveals the adaptability of a surface-exposed loop bearing Y62, H63, G64 and Y65 ( the YHGY loop) that is an integral part of the substrate and inhibitor binding pocket. This adaptability is important for accommodating inhibitors with variations in size. When compared with the human isozymes, this loop either becomes buried in the human type I enzyme due to an N-terminal extension that covers its position or is replaced by a unique insert in the human type II enzyme. Conclusion: The adaptability of the YHGY loop in E. coli methionine aminopeptidase, and likely in other bacterial methionine aminopeptidases, enables the enzyme active pocket to accommodate inhibitors of differing size. The differences in this adaptable loop between the bacterial and human methionine aminopeptidases is a structural feature that can be exploited to design inhibitors of bacterial methionine aminopeptidases as therapeutic agents with minimal inhibition of the corresponding human enzymes.
WOS关键词SACCHAROMYCES-CEREVISIAE ; IDENTIFICATION ; FUMAGILLIN ; OVALICIN ; TARGET ; MECHANISM ; CATALYSIS ; PROTEINS ; COFACTOR ; GENE
资助项目NCRR NIH HHS[P20 RR015563] ; NCRR NIH HHS[RR016475] ; NCRR NIH HHS[P20 RR017708] ; NCRR NIH HHS[P20 RR016475] ; NCRR NIH HHS[RR015563] ; NCRR NIH HHS[RR017708] ; NIAID NIH HHS[R56 AI065898] ; NIAID NIH HHS[AI065898] ; NIAID NIH HHS[R01 AI065898]
WOS研究方向Biophysics
语种英语
WOS记录号WOS:000253051600001
出版者BIOMED CENTRAL LTD
源URL[http://119.78.100.183/handle/2S10ELR8/273092]  
专题国家新药筛选中心
通讯作者Ye, Qi-Zhuang
作者单位1.Univ Kansas, High Throughput Screening Lab, Lawrence, KS 66047 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		 Ma, Ze-Qiang,Xie, Sheng-Xue,Huang, Qing-Qing,et al. Structural analysis of inhibition of E-coli methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes[J]. BMC STRUCTURAL BIOLOGY,2007,7.
APA Ma, Ze-Qiang,Xie, Sheng-Xue,Huang, Qing-Qing,Nan, Fa-Jun,Hurley, Thomas D.,&Ye, Qi-Zhuang.(2007).Structural analysis of inhibition of E-coli methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes.BMC STRUCTURAL BIOLOGY,7.
MLA Ma, Ze-Qiang,et al."Structural analysis of inhibition of E-coli methionine aminopeptidase: implication of loop adaptability in selective inhibition of bacterial enzymes".BMC STRUCTURAL BIOLOGY 7(2007).

入库方式： OAI收割

来源：上海药物研究所

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。