The applications of binuclear metallohydrolases in medicine: Recent advances in the design and development of novel drug leads for purple acid phosphatases, metallo-β-lactamases and arginases

被引：39

作者：

McGeary, Ross P. ^{[1
]}

Schenk, Gerhard ^{[1
]}

Guddat, Luke W. ^{[1
]}

机构：

[1] Univ Queensland, Sch Chem & Mol Biosci, St Lucia, Qld 4072, Australia

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 76卷

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

Metalloenzymes; Drug development; Osteoporosis; Antibiotic; STANDARD NUMBERING SCHEME; CRYSTAL-STRUCTURE; BACILLUS-CEREUS; BACTEROIDES-FRAGILIS; ACTIVE-SITE; KIDNEY ARGINASE; RAT-LIVER; BIOCHEMICAL-CHARACTERIZATION; 3-DIMENSIONAL STRUCTURE; PSEUDOMONAS-AERUGINOSA;

D O I：

10.1016/j.ejmech.2014.02.008

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Binuclear metallohydrolases are a family of proteins that can be targeted for drug discovery. The common feature of these enzymes is the presence of two closely spaced metal ions (i.e. less than 4 angstrom apart) that capture a water molecule that is used as a nucleophile in highly specific hydrolytic reactions. In this mini-review we describe what is known about the biological and catalytic activity, three-dimensional structure and inhibition for three prominent drug targets in this family of enzymes, (i) purple acid phosphatases, (ii) metallo-beta-lactamases and (iii) arginases. These enzymes are targets for the development of chemotherapeutics to treat a range of disorders including osteoporosis, cardiovascular disease and erectile dysfunctions, but also to stem the spread of antibiotic resistance, a major threat to global health care. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：132 / 144

页数：13