title: Metallo-beta-lactamases: two binding sites for one catalytic metal ion?
abstract: During the past few years the results from molecular biological, biochemical, chemical, physical and theoretical approaches expanded the knowledge about metallo-beta-lactamases considerably. The main reason for the attracted interest is a persisting medical problem. Bacteria expressing metallo-beta-lactamases can be resistant to treatment with all the known beta-lactam antibiotics, and they are additionally invulnerable to combined treatment with inhibitors for the wider-spread serine-beta-lactamases. However, clinically useful inhibitors for metallo-beta-lactamases are not yet available. In spite of the rapidly expanding knowledge base a central question is still controversially discussed: is it the mononuclear, the binuclear or the metal-free state which might serve as the physiologically relevant target for inhibitor design? A summary of the present views of the roles and coordination geometries of metal ion(s) in metallo-beta-lactamases is combined with a discussion of the possibly variable metal ion content under physiological conditions.
authors.affiliation: Department of Natural Sciences, The Royal Veterinary and Agricultural University, 1871, Frederiksberg C, Denmark. uwe@dina.kvl.dk
authors.forename: U
authors.initials: U
authors.lastname: Heinz
authors.forename: H-W
authors.initials: HW
authors.lastname: Adolph
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002384:Catalysis; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004795:Enzyme Stability; D007477:Ions; D008670:Metals / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D015032:Zinc / Q000737:chemistry / Q000378:metabolism; D018440:beta-Lactam Resistance; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D007477:Ions; D008670:Metals; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases; D015032:Zinc