1xa7
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(New page: 200px<br /><applet load="1xa7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xa7, resolution 2.40Å" /> '''Crystal structure of...)
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Revision as of 03:48, 21 November 2007
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Crystal structure of the benzylpenicillin-acylated BlaR1 sensor domain from Staphylococcus aureus
Overview
Staphylococcus aureus is among the most prevalent and antibiotic-resistant, of pathogenic bacteria. The resistance of S. aureus to prototypal, beta-lactam antibiotics is conferred by two mechanisms: (i) secretion of, hydrolytic beta-lactamase enzymes and (ii) production of, beta-lactam-insensitive penicillin-binding proteins (PBP2a). Despite their, distinct modes of resistance, expression of these proteins is controlled, by similar regulation systems, including a repressor (BlaI/MecI) and a, multidomain transmembrane receptor (BlaR1/MecR1). Resistance is triggered, in response to a covalent binding event between a beta-lactam antibiotic, and the extracellular sensor domain of BlaR1/MecR1 by transduction of the, binding signal to an intracellular protease domain capable of repressor, inactivation. This study describes the first crystal structures of the, sensor domain of BlaR1 (BlaRS) from S. aureus in both the apo and, penicillin-acylated forms. The structures show that the sensor domain, resembles the beta-lactam-hydrolyzing class D beta-lactamases, but is, rendered a penicillin-binding protein due to the formation of a very, stable acyl-enzyme. Surprisingly, conformational changes upon penicillin, binding were not observed in our structures, supporting the hypothesis, that transduction of the antibiotic-binding signal into the cytosol is, mediated by additional intramolecular interactions of the sensor domain, with an adjacent extracellular loop in BlaR1.
About this Structure
1XA7 is a Single protein structure of sequence from Staphylococcus aureus. Full crystallographic information is available from OCA.
Reference
Crystal structures of the Apo and penicillin-acylated forms of the BlaR1 beta-lactam sensor of Staphylococcus aureus., Wilke MS, Hills TL, Zhang HZ, Chambers HF, Strynadka NC, J Biol Chem. 2004 Nov 5;279(45):47278-87. Epub 2004 Aug 18. PMID:15322076
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