title: Inhibition of HIV-1 proteinase by metal ions.
abstract: 1. Certain metal ions have been identified as inhibitors (IC50 1-20 microM) of the aspartic proteinase of Human Immunodeficiency Virus Type 1 (HIV-PR). 2. By contrast most simple metal ions do not inhibit this enzyme. 3. Those that did inhibit have in common a high charge/size ratio or "hard" acidic nature, preferring to combine covalently with oxygen donor ligands. 4. Some evidence from independent X-ray crystal structure determinations suggests that the metalloinhibitors identified here may bind in the active site of the enzyme via coordination to the carboxylate side chains of the essential active site residues Asp 25 and 125. 5. Although the measured inhibition is only microM, very few enzyme-inhibitor interactions can be taking place and so more complex metalloinhibitors with ligands that can also bind to peptide side chains of the enzyme might be significantly more potent inhibitors of HIV-PR and of viral replication.
authors.affiliation: Centre for Drug Design and Development, University of Queensland, Australia.
authors.forename: T C
authors.initials: TC
authors.lastname: Woon
authors.forename: R I
authors.initials: RI
authors.lastname: Brinkworth
authors.forename: D P
authors.initials: DP
authors.lastname: Fairlie
mesh_terms: D000595:Amino Acid Sequence; D017320:HIV Protease Inhibitors; D008670:Metals / Q000494:pharmacology*; D008969:Molecular Sequence Data
chemical_list: D017320:HIV Protease Inhibitors; D008670:Metals