1xkz
From Proteopedia
(New page: 200px<br /><applet load="1xkz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xkz, resolution 1.75Å" /> '''Crystal structure of...) |
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| - | [[Image:1xkz.gif|left|200px]]<br /><applet load="1xkz" size=" | + | [[Image:1xkz.gif|left|200px]]<br /><applet load="1xkz" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1xkz, resolution 1.75Å" /> | caption="1xkz, resolution 1.75Å" /> | ||
'''Crystal structure of the acylated beta-lactam sensor domain of Blar1 from S. aureus'''<br /> | '''Crystal structure of the acylated beta-lactam sensor domain of Blar1 from S. aureus'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Methicillin-resistant strains of Staphylococcus aureus (MRSA) are the major cause of infections worldwide. Transcription of the -lactamase and PBP2a resistance genes is mediated by two closely related signal-transducing integral membrane proteins, BlaR1 and MecR1, upon binding of the -lactam inducer to the sensor domain. Herein we report the crystal structure at 1.75 | + | Methicillin-resistant strains of Staphylococcus aureus (MRSA) are the major cause of infections worldwide. Transcription of the beta-lactamase and PBP2a resistance genes is mediated by two closely related signal-transducing integral membrane proteins, BlaR1 and MecR1, upon binding of the beta-lactam inducer to the sensor domain. Herein we report the crystal structure at 1.75 A resolution of the sensor domain of BlaR1 in complex with a cephalosporin antibiotic. Activation of the signal transducer involves acylation of serine 389 by the beta-lactam antibiotic, a process promoted by the N-carboxylated side chain of Lys392. We present evidence that, on acylation, the lysine side chain experiences a spontaneous decarboxylation that entraps the sensor in its activated state. Kinetic determinations and quantum mechanical/molecular mechanical calculations and the interaction networks in the crystal structure shed light on how this unprecedented process for activation of a receptor may be achieved and provide insights into the mechanistic features that differentiate the signal-transducing receptor from the structurally related class D beta-lactamases, enzymes of antibiotic resistance. |
==About this Structure== | ==About this Structure== | ||
| - | 1XKZ 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 SO4, CAZ and EPE as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1XKZ 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=SO4:'>SO4</scene>, <scene name='pdbligand=CAZ:'>CAZ</scene> and <scene name='pdbligand=EPE:'>EPE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XKZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Staphylococcus aureus]] | [[Category: Staphylococcus aureus]] | ||
[[Category: Birck, C.]] | [[Category: Birck, C.]] | ||
| - | [[Category: Cha, J | + | [[Category: Cha, J Y.]] |
[[Category: Cross, J.]] | [[Category: Cross, J.]] | ||
| - | [[Category: Meroueh, S | + | [[Category: Meroueh, S O.]] |
[[Category: Mobashery, S.]] | [[Category: Mobashery, S.]] | ||
| - | [[Category: Samama, J | + | [[Category: Samama, J P.]] |
| - | [[Category: Schlegel, H | + | [[Category: Schlegel, H B.]] |
[[Category: Schulze-Briese, C.]] | [[Category: Schulze-Briese, C.]] | ||
[[Category: CAZ]] | [[Category: CAZ]] | ||
| Line 27: | Line 27: | ||
[[Category: signal transduction]] | [[Category: signal transduction]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:55:52 2008'' |
Revision as of 13:55, 21 February 2008
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Crystal structure of the acylated beta-lactam sensor domain of Blar1 from S. aureus
Overview
Methicillin-resistant strains of Staphylococcus aureus (MRSA) are the major cause of infections worldwide. Transcription of the beta-lactamase and PBP2a resistance genes is mediated by two closely related signal-transducing integral membrane proteins, BlaR1 and MecR1, upon binding of the beta-lactam inducer to the sensor domain. Herein we report the crystal structure at 1.75 A resolution of the sensor domain of BlaR1 in complex with a cephalosporin antibiotic. Activation of the signal transducer involves acylation of serine 389 by the beta-lactam antibiotic, a process promoted by the N-carboxylated side chain of Lys392. We present evidence that, on acylation, the lysine side chain experiences a spontaneous decarboxylation that entraps the sensor in its activated state. Kinetic determinations and quantum mechanical/molecular mechanical calculations and the interaction networks in the crystal structure shed light on how this unprecedented process for activation of a receptor may be achieved and provide insights into the mechanistic features that differentiate the signal-transducing receptor from the structurally related class D beta-lactamases, enzymes of antibiotic resistance.
About this Structure
1XKZ is a Single protein structure of sequence from Staphylococcus aureus with , and as ligands. Full crystallographic information is available from OCA.
Reference
X-ray crystal structure of the acylated beta-lactam sensor domain of BlaR1 from Staphylococcus aureus and the mechanism of receptor activation for signal transduction., Birck C, Cha JY, Cross J, Schulze-Briese C, Meroueh SO, Schlegel HB, Mobashery S, Samama JP, J Am Chem Soc. 2004 Nov 3;126(43):13945-7. PMID:15506754
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