1xkz

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{{STRUCTURE_1xkz| PDB=1xkz | SCENE= }}
{{STRUCTURE_1xkz| PDB=1xkz | SCENE= }}
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'''Crystal structure of the acylated beta-lactam sensor domain of Blar1 from S. aureus'''
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===Crystal structure of the acylated beta-lactam sensor domain of Blar1 from S. aureus===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_15506754}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 15506754 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15506754}}
==About this Structure==
==About this Structure==
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[[Category: Beta-lactam receptor]]
[[Category: Beta-lactam receptor]]
[[Category: Signal transduction]]
[[Category: Signal transduction]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 15:10:00 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 02:21:22 2008''

Revision as of 23:21, 27 July 2008

Image:1xkz.png

Template:STRUCTURE 1xkz

Crystal structure of the acylated beta-lactam sensor domain of Blar1 from S. aureus

Template:ABSTRACT PUBMED 15506754

About this Structure

1XKZ is a Single protein structure of sequence from Staphylococcus aureus. 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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