Disease relevance of blaR1

• We report herein a kinetic and structural study, obtained by stopped-flow IR spectroscopy, of the activation of the BlaR1 receptor of the Staphylococcus aureus bacterium by beta-lactam antibiotics [1].

High impact information on blaR1

• The cell-surface BlaR1 receptor alerts the bacterium to the presence of beta-lactam antibiotics, resulting in expression of the gene for a beta-lactamase enzyme [1].
• The key chemical events in beta-lactam recognition are serine acylation and subsequent irreversible decarboxylation of the BlaR1 active site lysine carbamate [1].
• Discrete steps in sensing of beta-lactam antibiotics by the BlaR1 protein of the methicillin-resistant Staphylococcus aureus bacterium [1].
• Surprisingly, conformational changes upon penicillin binding were not observed in our structures, supporting the hypothesis that transduction of the antibiotic-binding signal into the cytosol is mediated by additional intramolecular interactions of the sensor domain with an adjacent extracellular loop in BlaR1 [2].
• The beta-lactam sensor-transducer (BlaR), an integral membrane protein, binds beta-lactam antibiotics on the cell surface and transduces the information to the cytoplasm, where gene expression is derepressed for both beta-lactamase and penicillin-binding protein 2a [3].

Chemical compound and disease context of blaR1

• Lysine N(zeta)-Decarboxylation in the BlaR1 Protein from Staphylococcus aureus at the Root of Its Function As an Antibiotic Sensor [4].

Biological context of blaR1

• As such, BlaR1 experience acylation by the antibiotic that it senses, an event that enjoys longevity for at least the duration of one bacterial generation [4].
• The structure of the surface domain of the BlaR1 protein of Staphylococcus aureus, a beta-lactam antibiotic sensor/signal transducer, is essentially identical to that of the class D beta-lactamases, which are antibiotic resistance enzymes [4].
• Two residues of the BlaR C-terminal domain, Thr452 and Thr542, modify the hydrophobic characteristic of the class D beta-lactamase active site [5].

Associations of blaR1 with chemical compounds

• We report herein the production of S-(4-butanoate)-cysteine, as a surrogate of N-carboxylated lysine at position 392 of the BlaR1 protein [4].
• Therefore we investigated the possibility that BlaR1 might be the main target for PDO action [6].
• Our results demonstrate that BlaR1 could be an attractive new target for the development of new drugs to overcome methicillin resistance [6].

References