Crystal structure of a phosphonotripeptide K-26 in complex with angiotensin converting enzyme homologue (AnCE) from Drosophila melanogaster

被引：17

作者：

Akif, Mohd ^{[1
]}

Ntai, Ioanna ^{[2
]}

Sturrock, Edward D. ^{[3
,4
]}

Isaac, R. Elwyn ^{[5
]}

Bachmann, Brian O. ^{[6
]}

Acharya, K. Ravi ^{[1
]}

机构：

[1] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England

[2] Univ Illinois, Urbana, IL 61801 USA

[3] Univ Cape Town, Div Med Biochem, ZA-7925 Observatory, South Africa

[4] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Observatory, South Africa

[5] Univ Leeds, Fac Biol Sci, Inst Integrat & Comparat Biol, Leeds LS2 9JT, W Yorkshire, England

[6] Vanderbilt Univ, Dept Chem, Nashville, TN 37235 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2010年 / 398卷 / 03期

基金：

英国医学研究理事会;

关键词：

Angiotensin converting enzyme; Zinc metallopeptidase; X-ray crystallography; Inhibitor binding; Drosophila melanogaster; C-DOMAIN; SELECTIVE INHIBITOR; N-DOMAIN; IDENTIFICATION; RESEMBLES; SUBSTRATE; CAPTOPRIL; PEPTIDE; BINDING; POTENT;

D O I：

10.1016/j.bbrc.2010.06.113

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Angiotensin-I converting enzyme (ACE, a zinc dependent dipeptidyl carboxypeptidase) is a major target of drugs due to its role in the modulation of blood pressure and cardiovascular disorders. Here we present a crystal structure of AnCE (an ACE homologue from Drosophila melanogaster with a single enzymatic domain) in complex with a natural product-phosphonotripeptide. K-26 at 1.96 angstrom resolution. The inhibitor binds exclusively in the S-1 and S-2 binding pockets of AnCE (coordinating the zinc ion) through ionic and hydrogen bond interactions. A detailed structural comparison of AnCE-K-26 complex with individual domains of human somatic ACE provides useful information for further exploration of ACE inhibitor pharmacophores involving phosphonic acids. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：532 / 536

页数：5

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