1NRF

C-terminal domain of the Bacillus licheniformis BlaR penicillin-receptor

Summary for 1NRF

• Entry DOI: 10.2210/pdb1nrf/pdb
• Descriptor: REGULATORY PROTEIN BLAR1 (2 entities in total)
• Functional Keywords: penicillin-receptor, beta-lactamase induction, bacillus licheniformis, penicillin-binding protein, membrane protein
• Biological source: Bacillus licheniformis
• Cellular location: Cell membrane; Multi-pass membrane protein (Probable): P12287
• Total number of polymer chains: 1
• Total formula weight: 29902.07

Authors

Kerff, F.,Charlier, P.,Columbo, M.L.,Sauvage, E.,Brans, A.,Frere, J.M.,Joris, B.,Fonze, E. (deposition date: 2003-01-24, release date: 2004-01-24, Last modification date: 2024-04-03)

Primary citation

Kerff, F.,Charlier, P.,Colombo, M.L.,Sauvage, E.,Brans, A.,Frere, J.M.,Joris, B.,Fonze, E.
Crystal structure of the sensor domain of the BlaR penicillin receptor from Bacillus licheniformis.
Biochemistry, 42:12835-12843, 2003

PubMed Abstract: As in several staphylococci, the synthesis of the Bacillus licheniformis 749/I beta-lactamase is an inducible phenomenon regulated by a signal-transducing membrane protein BlaR. The C-terminal domain of this multimodular protein is an extracellular domain which specifically recognizes beta-lactam antibiotics. When it binds a beta-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 of reactions is generated, leading to the transcription of the beta-lactamase gene. Here, we describe the crystal structure of the extracellular penicillin-receptor domain of BlaR (residues 346-601) at 2.5 A resolution in order to understand why this domain, whose folding is very similar to that of class D beta-lactamases, behaves as a highly sensitive penicillin-binding protein rather than a beta-lactamase. Two residues of the BlaR C-terminal domain, Thr452 and Thr542, modify the hydrophobic characteristic of the class D beta-lactamase active site. Both residues seem to be in part responsible for the lack of beta-lactamase activity of the BlaR protein due to the stability of the acyl-enzyme. Although further experimental data are needed to fully understand the transmembrane induction process, the comparison of the BlaR sensor domain structure with those of class D beta-lactamase complexes and penicillin-binding proteins provides interesting elements to hypothesize on possible signal transmission mechanisms.

PubMed: 14596597
DOI: 10.1021/bi034976a

Experimental method

X-RAY DIFFRACTION (2.5 Å)