1xa1
From Proteopedia
(New page: 200px<br /><applet load="1xa1" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xa1, resolution 1.80Å" /> '''Crystal structure of...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1xa1.gif|left|200px]]<br /><applet load="1xa1" size=" | + | [[Image:1xa1.gif|left|200px]]<br /><applet load="1xa1" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1xa1, resolution 1.80Å" /> | caption="1xa1, resolution 1.80Å" /> | ||
'''Crystal structure of the sensor domain of BlaR1 from Staphylococcus aureus in its apo form'''<br /> | '''Crystal structure of the sensor domain of BlaR1 from Staphylococcus aureus in its apo form'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Staphylococcus aureus is among the most prevalent and antibiotic-resistant | + | 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== | ==About this Structure== | ||
| - | 1XA1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with PO4 and POP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1XA1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus] with <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=POP:'>POP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XA1 OCA]. |
==Reference== | ==Reference== | ||
| Line 13: | Line 13: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Staphylococcus aureus]] | [[Category: Staphylococcus aureus]] | ||
| - | [[Category: Chambers, H | + | [[Category: Chambers, H F.]] |
| - | [[Category: Hills, T | + | [[Category: Hills, T L.]] |
| - | [[Category: Strynadka, N | + | [[Category: Strynadka, N C.]] |
| - | [[Category: Wilke, M | + | [[Category: Wilke, M S.]] |
| - | [[Category: Zhang, H | + | [[Category: Zhang, H Z.]] |
[[Category: PO4]] | [[Category: PO4]] | ||
[[Category: POP]] | [[Category: POP]] | ||
| Line 26: | Line 26: | ||
[[Category: staphylococcus aureus]] | [[Category: staphylococcus aureus]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:52:36 2008'' |
Revision as of 13:52, 21 February 2008
|
Crystal structure of the sensor domain of BlaR1 from Staphylococcus aureus in its apo form
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
1XA1 is a Single protein structure of sequence from Staphylococcus aureus with and as ligands. 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
Page seeded by OCA on Thu Feb 21 15:52:36 2008
