Crystal Structure of the Sensor Domain of the BlaR Penicillin Receptor from Bacillus licheniformis
详细信息 查看全文
- 作者：Fré ; dé ; ric Kerff ; Paulette Charlier ; Maria-Luigi Colombo ; Eric Sauvage ; Alain Brans ; Jean-Marie Frè ; re ; Bernard Joris ; and Eveline Fonzé
- 刊名：Biochemistry
- 出版年：2003
- 出版时间：November 11, 2003
- 年：2003
- 卷：42
- 期：44
- 页码：12835 - 12843
- 全文大小：806K
- 年卷期：v.42,no.44(November 11, 2003)
- ISSN：1520-4995
文摘
As in several staphylococci, the synthesis of the Bacillus licheniformis 749/I 
-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 -lactam antibiotics.When it binds a -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 -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 -lactamases,behaves as a highly sensitive penicillin-binding protein rather than a -lactamase. Two residues of theBlaR C-terminal domain, Thr452 and Thr542, modify the hydrophobic characteristic of the class D-lactamase active site. Both residues seem to be in part responsible for the lack of -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 -lactamase complexes and penicillin-binding proteins provides interestingelements to hypothesize on possible signal transmission mechanisms.
-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 -lactam antibiotics.When it binds a -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 -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 -lactamases,behaves as a highly sensitive penicillin-binding protein rather than a -lactamase. Two residues of theBlaR C-terminal domain, Thr452 and Thr542, modify the hydrophobic characteristic of the class D-lactamase active site. Both residues seem to be in part responsible for the lack of -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 -lactamase complexes and penicillin-binding proteins provides interestingelements to hypothesize on possible signal transmission mechanisms.