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| ==BlaR1 sensor domain from Staphylococcus aureus with N439V mutation== | | ==BlaR1 sensor domain from Staphylococcus aureus with N439V mutation== |
| <StructureSection load='3uy6' size='340' side='right' caption='[[3uy6]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='3uy6' size='340' side='right'caption='[[3uy6]], [[Resolution|resolution]] 2.10Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3uy6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UY6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UY6 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3uy6]] is a 2 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=3UY6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UY6 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3q7v|3q7v]], [[3q81|3q81]], [[3q82|3q82]]</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3uy6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uy6 OCA], [https://pdbe.org/3uy6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uy6 RCSB], [https://www.ebi.ac.uk/pdbsum/3uy6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uy6 ProSAT]</span></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3uy6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uy6 OCA], [http://pdbe.org/3uy6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3uy6 RCSB], [http://www.ebi.ac.uk/pdbsum/3uy6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3uy6 ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/BLAR_STAAU BLAR_STAAU]] BlaR1 is a potential penicillin-binding protein required for induction of beta-lactamase. | | [https://www.uniprot.org/uniprot/BLAR_STAAU BLAR_STAAU] BlaR1 is a potential penicillin-binding protein required for induction of beta-lactamase. |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The integral membrane protein BlaR1 of Staphylococcus aureus senses the presence of beta-lactam antibiotics in the milieu and transduces the information to its cytoplasmic side, where its activity unleashes the expression of a set of genes, including that for BlaR1 itself, which manifest the antibiotic-resistant phenotype. The x-ray structure of the sensor domain of this protein exhibits an uncanny similarity to those of the class D beta-lactamases. The former is a membrane-bound receptor/sensor for the beta-lactam antibiotics, devoid of catalytic competence for substrate turnover, whereas the latter are soluble periplasmic enzymes in gram-negative bacteria with avid ability for beta-lactam turnover. The two are clearly related to each other from an evolutionary point of view. However, the high resolution x-ray structures for both by themselves do not reveal why one is a receptor and the other an enzyme. It is documented herein that a single amino acid change at position 439 of the BlaR1 protein is sufficient to endow the receptor/sensor protein with modest turnover ability for cephalosporins as substrates. The x-ray structure for this mutant protein and the dynamics simulations revealed how a hydrolytic water molecule may sequester itself in the antibiotic-binding site to enable hydrolysis of the acylated species. These studies document how the nature of the residue at position 439 is critical for the fate of the protein in imparting unique functions on the same molecular template, to result in one as a receptor and in another as a catalyst.
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| An amino acid position at crossroads of evolution of protein function: antibiotic sensor domain of BlaR1 protein from Staphylococcus aureus versus clasS D beta-lactamases.,Kumarasiri M, Llarrull LI, Borbulevych O, Fishovitz J, Lastochkin E, Baker BM, Mobashery S J Biol Chem. 2012 Mar 9;287(11):8232-41. Epub 2012 Jan 18. PMID:22262858<ref>PMID:22262858</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 3uy6" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Baker, B M]] | | [[Category: Large Structures]] |
| [[Category: Borbulevych, O Y]] | | [[Category: Staphylococcus aureus]] |
| [[Category: Antibiotic sensor protein]] | | [[Category: Baker BM]] |
| [[Category: Penicillin-binding protein]] | | [[Category: Borbulevych OY]] |