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

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.