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

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• 作者：Ross P. McGeary ; ^{r.mcgeary@uq.edu.au" class="auth_mail} ; Gerhard Schenk ^{schenk@uq.edu.au" class="auth_mail gerhardschenk@gmail.com" class="auth_mail} ; Luke W. Guddat ; ^{luke.guddat@uq.edu.au" class="auth_mail}
• 关键词：Metalloenzymes ; Drug development ; Osteoporosis ; Antibiotic
• 刊名：European Journal of Medicinal Chemistry
• 出版年：9 April, 2014
• 年：2014
• 卷：76
• 期：Complete
• 页码：132-144
• 全文大小：2261 K

文摘

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聽脜 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-尾-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.