| Abstract
| - As in several staphylococci, the synthesis of the Bacillus licheniformis 749/I β-lactamase isan inducible phenomenon regulated by a signal-transducing membrane protein BlaR. The C-terminal domainof this multimodular protein is an extracellular domain which specifically recognizes β-lactam antibiotics.When it binds a β-lactam, a signal is transmitted by the transmembrane region to the intracellular loops.In response, the hydrolytic activity of the BlaR large cytoplasmic L3 loop is induced, and a cascade ofreactions is generated, leading to the transcription of the β-lactamase gene. Here, we describe the crystalstructure of the extracellular penicillin-receptor domain of BlaR (residues 346−601) at 2.5 Å resolutionin order to understand why this domain, whose folding is very similar to that of class D β-lactamases,behaves as a highly sensitive penicillin-binding protein rather than a β-lactamase. Two residues of theBlaR C-terminal domain, Thr452 and Thr542, modify the hydrophobic characteristic of the class Dβ-lactamase active site. Both residues seem to be in part responsible for the lack of β-lactamase activityof the BlaR protein due to the stability of the acyl-enzyme. Although further experimental data are neededto fully understand the transmembrane induction process, the comparison of the BlaR sensor domainstructure with those of class D β-lactamase complexes and penicillin-binding proteins provides interestingelements to hypothesize on possible signal transmission mechanisms.
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