title: 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.
abstract: 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 Å 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-β-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.
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, St. Lucia, QLD 4072, Australia. Electronic address: r.mcgeary@uq.edu.au.
authors.forename: Ross P
authors.initials: RP
authors.lastname: McGeary
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, St. Lucia, QLD 4072, Australia. Electronic address: schenk@uq.edu.au.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schenk
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, St. Lucia, QLD 4072, Australia. Electronic address: luke.guddat@uq.edu.au.
authors.forename: Luke W
authors.initials: LW
authors.lastname: Guddat
mesh_terms: D000135:Acid Phosphatase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006867:Hydrolases / Q000187:drug effects*; D008667:Metalloproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D006023:Glycoproteins; D008667:Metalloproteins; D065093:beta-Lactamase Inhibitors; D006867:Hydrolases; C091137:purple acid phosphatase; D000135:Acid Phosphatase; D001618:beta-Lactamases; D001119:Arginase
keywords: Antibiotic; Drug development; Metalloenzymes; Osteoporosis