Characterization of the -Lactam Antibiotic Sensor Domain of the MecR1 Signal Sensor/Transducer Protein from Methicill
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- 作者：Jooyoung Cha ; Sergei B. Vakulenko ; Shahriar Mobashery
- 刊名：Biochemistry
- 出版年：2007
- 出版时间：July 3, 2007
- 年：2007
- 卷：46
- 期：26
- 页码：7822 - 7831
- 全文大小：555K
- 年卷期：v.46,no.26(July 3, 2007)
- ISSN：1520-4995
文摘
Methicillin-resistant Staphylococcus aureus (MRSA) has evolved two mechanisms for resistanceto 
beta2.gif" BORDER=0 ALIGN="middle">-lactam antibiotics. One is production of a beta2.gif" BORDER=0 ALIGN="middle">-lactamase, and the other is that of penicillin-bindingprotein 2a (PBP 2a). The expression of these two proteins is regulated by the bla and mec operons,respectively. BlaR1 and MecR1 are beta2.gif" BORDER=0 ALIGN="middle">-lactam sensor/signal transducer proteins, which experience acylationby beta2.gif" BORDER=0 ALIGN="middle">-lactam antibiotics on the cell surface and transduce the signal into the cytoplasm. The C-terminalsurface domain of MecR1 (MecRS) has been cloned, expressed, and purified to homogeneity. This proteinhas been characterized by documenting that it has a critical and unusual N
-carboxylated lysine at position394. Furthermore, the kinetics of interactions with beta2.gif" BORDER=0 ALIGN="middle">-lactam antibiotics were evaluated, a process thatentails conformational changes for the protein that might be critical for the signal transduction event.Kinetics of acylation of MecRS are suggestive that signal sensing may be the step where the two systemsare substantially different from one another.
beta2.gif" BORDER=0 ALIGN="middle">-lactam antibiotics. One is production of a beta2.gif" BORDER=0 ALIGN="middle">-lactamase, and the other is that of penicillin-bindingprotein 2a (PBP 2a). The expression of these two proteins is regulated by the bla and mec operons,respectively. BlaR1 and MecR1 are beta2.gif" BORDER=0 ALIGN="middle">-lactam sensor/signal transducer proteins, which experience acylationby beta2.gif" BORDER=0 ALIGN="middle">-lactam antibiotics on the cell surface and transduce the signal into the cytoplasm. The C-terminalsurface domain of MecR1 (MecRS) has been cloned, expressed, and purified to homogeneity. This proteinhas been characterized by documenting that it has a critical and unusual N-carboxylated lysine at position394. Furthermore, the kinetics of interactions with beta2.gif" BORDER=0 ALIGN="middle">-lactam antibiotics were evaluated, a process thatentails conformational changes for the protein that might be critical for the signal transduction event.Kinetics of acylation of MecRS are suggestive that signal sensing may be the step where the two systemsare substantially different from one another.