title: Promiscuous metallo-β-lactamases: MIM-1 and MIM-2 may play an essential role in quorum sensing networks.
abstract: MIM-1 and MIM-2 are two recently identified metallo-β-lactamases (MBLs) from Novosphingobium pentaromativorans and Simiduia agarivorans, respectively. Since these organisms are non-pathogenic we speculated that the biological role(s) of MIM-1 and MIM-2 may not be related to their MBL activity. Although both sequence comparison and homology modeling indicate that these proteins are homologous to well-known MBLs such as AIM-1, the sequence analysis also indicated that MIM-1 and MIM-2 share similarities with N-acyl homoserine lactonases (AHLases) and glyoxalase II (GLX-II). Steady-state kinetic assays using a series of lactone substrates confirm that MIM-1 and MIM-2 are efficient lactonases, with catalytic efficiencies resembling those of well-known AHLases. Interestingly, unlike their MBL activity the AHLase activity of MIM-1 and MIM-2 is not dependent on the metal ion composition with Zn(II), Co(II), Cu(II), Mn(II) and Ca(II) all being able to reconstitute catalytic activity (with Co(II) being the most efficient). However, these enzymes do not turn over S-lactoylglutathione, a substrate characteristic for GLX-II activity. Since lactonase activity is linked to the process of quorum sensing the bifunctional activity of "non-pathogenic" MBLs such as MIM-1 and MIM-2 may provide insight into one possible evolutionary pathway for the emergence of antibiotic resistance.
authors.affiliation: Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland; School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Manfredi
authors.initials: M
authors.lastname: Miraula
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia. Electronic address: schenk@uq.edu.au.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schenk
authors.affiliation: Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland. Electronic address: natasa.mitic@nuim.ie.
authors.forename: Nataša
authors.initials: N
authors.lastname: Mitić
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000737:chemistry; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D003035:Cobalt / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005978:Glutathione / Q000031:analogs & derivatives; D007700:Kinetics; D008345:Manganese / Q000737:chemistry; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D011548:Pseudomonadaceae / Q000737:chemistry / Q000201:enzymology*; D053038:Quorum Sensing / Q000235:genetics*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D042301:Sphingomonadaceae / Q000737:chemistry / Q000201:enzymology*; D013379:Substrate Specificity; D013869:Thiolester Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000737:chemistry; D001618:beta-Lactamases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000099301:Hydroxyacylglutathione Hydrolase
chemical_list: D001426:Bacterial Proteins; D002118:Calcium; D002265:Carboxylic Ester Hydrolases; D003035:Cobalt; D003300:Copper; D005978:Glutathione; D008345:Manganese; D011994:Recombinant Proteins; D013869:Thiolester Hydrolases; D015032:Zinc; D001618:beta-Lactamases; D000099301:Hydroxyacylglutathione Hydrolase; C432003:N-acyl homoserine lactonase; C013585:S-lactoylglutathione
keywords: Antibiotic resistance; Binuclear metallohydrolases; Functional promiscuity; Metallo-beta-lactamases; Quorum sensing