1xkz

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(New page: 200px<br /><applet load="1xkz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xkz, resolution 1.75&Aring;" /> '''Crystal structure of...)
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[[Image:1xkz.gif|left|200px]]<br /><applet load="1xkz" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1xkz, resolution 1.75&Aring;" />
 
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'''Crystal structure of the acylated beta-lactam sensor domain of Blar1 from S. aureus'''<br />
 
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==Overview==
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==Crystal structure of the acylated beta-lactam sensor domain of Blar1 from S. aureus==
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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 &Aring; 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 -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 -lactamases, enzymes of antibiotic resistance.
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<StructureSection load='1xkz' size='340' side='right'caption='[[1xkz]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[1xkz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XKZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XKZ FirstGlance]. <br>
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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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1XKZ OCA].
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAZ:ACYLATED+CEFTAZIDIME'>CAZ</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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==Reference==
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1xkz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xkz OCA], [https://pdbe.org/1xkz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xkz RCSB], [https://www.ebi.ac.uk/pdbsum/1xkz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xkz ProSAT]</span></td></tr>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15506754 15506754]
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</table>
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[[Category: Single protein]]
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== Function ==
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[https://www.uniprot.org/uniprot/BLAR_STAAU BLAR_STAAU] BlaR1 is a potential penicillin-binding protein required for induction of beta-lactamase.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xk/1xkz_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1xkz ConSurf].
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<div style="clear:both"></div>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Staphylococcus aureus]]
[[Category: Staphylococcus aureus]]
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[[Category: Birck, C.]]
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[[Category: Birck C]]
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[[Category: Cha, J.Y.]]
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[[Category: Cha JY]]
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[[Category: Cross, J.]]
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[[Category: Cross J]]
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[[Category: Meroueh, S.O.]]
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[[Category: Meroueh SO]]
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[[Category: Mobashery, S.]]
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[[Category: Mobashery S]]
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[[Category: Samama, J.P.]]
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[[Category: Samama J-P]]
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[[Category: Schlegel, H.B.]]
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[[Category: Schlegel HB]]
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[[Category: Schulze-Briese, C.]]
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[[Category: Schulze-Briese C]]
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[[Category: CAZ]]
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[[Category: EPE]]
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[[Category: SO4]]
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[[Category: beta-lactam receptor]]
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[[Category: signal transduction]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 06:08:12 2007''
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Current revision

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

PDB ID 1xkz

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