This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
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...) |
|||
| Line 1: | Line 1: | ||
| - | [[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== | ||
| Line 14: | Line 14: | ||
[[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
|
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
Page seeded by OCA on Thu Feb 21 15:55:52 2008
