[en] 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 Angstrom 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Kerff, Frédéric ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Charlier, Paulette ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Colombo, Maria Louisa; Université de Liège - ULiège > Centre d'Ingénierie des Protéines
Sauvage, Eric ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Brans, Alain ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Frère, Jean-Marie ; Université de Liège - ULiège > Centre d'Ingénierie des Protéines
Joris, Bernard ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Fonze, Eveline; Université de Liège - ULiège > Centre d'Ingénierie des Protéines
Language :
English
Title :
Crystal structure of the sensor domain of the BlaR penicillin receptor from Bacillus licheniformis
Publication date :
11 November 2003
Journal title :
Biochemistry
ISSN :
0006-2960
eISSN :
1520-4995
Publisher :
Amer Chemical Soc, Washington, United States - Washington
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