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

  • Eur J Med Chem. 2014 Apr 9:76:132-44. doi: 10.1016/j.ejmech.2014.02.008.
Ross P McGeary  1 ,  Gerhard Schenk  2 ,  Luke W Guddat  3
Affiliations
  • 1. The University of Queensland, School of Chemistry and Molecular Biosciences, St. Lucia, QLD 4072, Australia. Electronic address: [email protected].
  • 2. The University of Queensland, School of Chemistry and Molecular Biosciences, St. Lucia, QLD 4072, Australia. Electronic address: [email protected].
  • 3. The University of Queensland, School of Chemistry and Molecular Biosciences, St. Lucia, QLD 4072, Australia. Electronic address: [email protected].
PMID: 24583353 DOI: 10.1016/j.ejmech.2014.02.008
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.

Keywords
Antibiotic; Drug development; Metalloenzymes; Osteoporosis.
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