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Title: Lysine N[superscript zeta]-Decarboxylation Switch and Activation of the [beta]-Lactam Sensor Domain of BlaR1 Protein of Methicillin-resistant Staphylococcus aureus

Abstract

The integral membrane protein BlaR1 of methicillin-resistant Staphylococcus aureus senses the presence of {beta}-lactam antibiotics in the milieu and transduces the information to the cytoplasm, where the biochemical events that unleash induction of antibiotic resistance mechanisms take place. We report herein by two-dimensional and three-dimensional NMR experiments of the sensor domain of BlaR1 in solution and by determination of an x-ray structure for the apo protein that Lys-392 of the antibiotic-binding site is posttranslationally modified by N{sup {zeta}}-carboxylation. Additional crystallographic and NMR data reveal that on acylation of Ser-389 by antibiotics, Lys-392 experiences N{sup {zeta}}-decarboxylation. This unique process, termed the lysine N{sup {zeta}}-decarboxylation switch, arrests the sensor domain in the activated ('on') state, necessary for signal transduction and all the subsequent biochemical processes. We present structural information on how this receptor activation process takes place, imparting longevity to the antibiotic-receptor complex that is needed for the induction of the antibiotic-resistant phenotype in methicillin-resistant S. aureus.

Authors:
; ; ; ; ; ; ; ; ;  [1]
  1. (Notre)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1046860
Resource Type:
Journal Article
Journal Name:
J. Biol. Chem.
Additional Journal Information:
Journal Volume: 286; Journal Issue: (36) ; 09, 2011; Journal ID: ISSN 0021-9258
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ACYLATION; ANTIBIOTICS; BACTERIA; CRYSTAL STRUCTURE; CYTOPLASM; INDUCTION; LYSINE; MEMBRANE PROTEINS; PHENOTYPE; PROTEINS; SENSORS; STAPHYLOCOCCUS

Citation Formats

Borbulevych, Oleg, Kumarasiri, Malika, Wilson, Brian, Llarrull1, Leticia I., Lee, Mijoon, Hesek, Dusan, Shi, Qicun, Peng, Jeffrey, Baker, Brian M., and Mobashery, Shahriar. Lysine N[superscript zeta]-Decarboxylation Switch and Activation of the [beta]-Lactam Sensor Domain of BlaR1 Protein of Methicillin-resistant Staphylococcus aureus. United States: N. p., 2012. Web. doi:10.1074/jbc.M111.252189.
Borbulevych, Oleg, Kumarasiri, Malika, Wilson, Brian, Llarrull1, Leticia I., Lee, Mijoon, Hesek, Dusan, Shi, Qicun, Peng, Jeffrey, Baker, Brian M., & Mobashery, Shahriar. Lysine N[superscript zeta]-Decarboxylation Switch and Activation of the [beta]-Lactam Sensor Domain of BlaR1 Protein of Methicillin-resistant Staphylococcus aureus. United States. doi:10.1074/jbc.M111.252189.
Borbulevych, Oleg, Kumarasiri, Malika, Wilson, Brian, Llarrull1, Leticia I., Lee, Mijoon, Hesek, Dusan, Shi, Qicun, Peng, Jeffrey, Baker, Brian M., and Mobashery, Shahriar. Mon . "Lysine N[superscript zeta]-Decarboxylation Switch and Activation of the [beta]-Lactam Sensor Domain of BlaR1 Protein of Methicillin-resistant Staphylococcus aureus". United States. doi:10.1074/jbc.M111.252189.
@article{osti_1046860,
title = {Lysine N[superscript zeta]-Decarboxylation Switch and Activation of the [beta]-Lactam Sensor Domain of BlaR1 Protein of Methicillin-resistant Staphylococcus aureus},
author = {Borbulevych, Oleg and Kumarasiri, Malika and Wilson, Brian and Llarrull1, Leticia I. and Lee, Mijoon and Hesek, Dusan and Shi, Qicun and Peng, Jeffrey and Baker, Brian M. and Mobashery, Shahriar},
abstractNote = {The integral membrane protein BlaR1 of methicillin-resistant Staphylococcus aureus senses the presence of {beta}-lactam antibiotics in the milieu and transduces the information to the cytoplasm, where the biochemical events that unleash induction of antibiotic resistance mechanisms take place. We report herein by two-dimensional and three-dimensional NMR experiments of the sensor domain of BlaR1 in solution and by determination of an x-ray structure for the apo protein that Lys-392 of the antibiotic-binding site is posttranslationally modified by N{sup {zeta}}-carboxylation. Additional crystallographic and NMR data reveal that on acylation of Ser-389 by antibiotics, Lys-392 experiences N{sup {zeta}}-decarboxylation. This unique process, termed the lysine N{sup {zeta}}-decarboxylation switch, arrests the sensor domain in the activated ('on') state, necessary for signal transduction and all the subsequent biochemical processes. We present structural information on how this receptor activation process takes place, imparting longevity to the antibiotic-receptor complex that is needed for the induction of the antibiotic-resistant phenotype in methicillin-resistant S. aureus.},
doi = {10.1074/jbc.M111.252189},
journal = {J. Biol. Chem.},
issn = {0021-9258},
number = (36) ; 09, 2011,
volume = 286,
place = {United States},
year = {2012},
month = {10}
}