Crystal structure of Drosophila angiotensin I‐converting enzyme bound to captopril and lisinopril 1

FEBS Letters

Lee, Hayyoung¹  Shin, Dong Ryeol²  Lee, Jie-Oh²  Kim, Ho Min³  Yoo, Ook Joon³ 

[1] Center for Biotechnology, Chungnam National University, Daejeon, South Korea;Department of Chemistry, Korea Advanced Institute of Science and Technology, 373-1 Kusong-dong, Yusong-gu, Daejeon, South Korea;Department of Biological Science, Korea Advanced Institute of Science and Technology, 373-1 Kusong-dong, Yusong-gu, Daejeon, South Korea

关键词: Angiotensin I-converting enzyme;    Angiotensin;    Captopril;    Lisinopril;    X-ray crystal structure;    ACE;    angiotensin I-converting enzyme;    NCS;    non-crystallographic symmetry;   

DOI  :  10.1016/S0014-5793(03)00128-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Angiotensin I-converting enzymes (ACEs) are zinc metallopeptidases that cleave carboxy-terminal dipeptides from short peptide hormones. We have determined the crystal structures of AnCE, a Drosophila homolog of ACE, with and without bound inhibitors to 2.4 Å resolution. AnCE contains a large internal channel encompassing the entire protein molecule. This substrate-binding channel is composed of two chambers, reminiscent of a peanut shell. The inhibitor and zinc-binding sites are located in the narrow bottleneck connecting the two chambers. The substrate and inhibitor specificity of AnCE appears to be determined by extensive hydrogen-bonding networks and ionic interactions in the active site channel. The catalytically important zinc ion is coordinated by the conserved Glu395 and histidine residues from a HExxH motif.

【 授权许可】

Unknown