title: Characterization of the beta-lactam antibiotic sensor domain of the MecR1 signal sensor/transducer protein from methicillin-resistant Staphylococcus aureus.
abstract: Methicillin-resistant Staphylococcus aureus (MRSA) has evolved two mechanisms for resistance to beta-lactam antibiotics. One is production of a beta-lactamase, and the other is that of penicillin-binding protein 2a (PBP 2a). The expression of these two proteins is regulated by the bla and mec operons, respectively. BlaR1 and MecR1 are beta-lactam sensor/signal transducer proteins, which experience acylation by beta-lactam antibiotics on the cell surface and transduce the signal into the cytoplasm. The C-terminal surface domain of MecR1 (MecRS) has been cloned, expressed, and purified to homogeneity. This protein has been characterized by documenting that it has a critical and unusual Nzeta-carboxylated lysine at position 394. Furthermore, the kinetics of interactions with beta-lactam antibiotics were evaluated, a process that entails conformational changes for the protein that might be critical for the signal transduction event. Kinetics of acylation of MecRS are suggestive that signal sensing may be the step where the two systems are substantially different from one another.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, USA.
authors.forename: Jooyoung
authors.initials: J
authors.lastname: Cha
authors.forename: Sergei B
authors.initials: SB
authors.lastname: Vakulenko
authors.forename: Shahriar
authors.initials: S
authors.lastname: Mobashery
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry; D002942:Circular Dichroism; D003001:Cloning, Molecular; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000378:metabolism; D007700:Kinetics; D008239:Lysine / Q000737:chemistry; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D046915:Penicillin-Binding Proteins / Q000737:chemistry; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D047090:beta-Lactams / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D047090:beta-Lactams; C101641:mecR1 protein, Staphylococcus aureus; D008239:Lysine