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| | ==Crystal structure of PBP2a clinical mutant E150K from MRSA== | | ==Crystal structure of PBP2a clinical mutant E150K from MRSA== |
| - | <StructureSection load='4bl2' size='340' side='right' caption='[[4bl2]], [[Resolution|resolution]] 2.72Å' scene=''> | + | <StructureSection load='4bl2' size='340' side='right'caption='[[4bl2]], [[Resolution|resolution]] 2.72Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4bl2]] 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=4BL2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BL2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4bl2]] 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=4BL2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BL2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.72Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bl3|4bl3]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Serine-type_D-Ala-D-Ala_carboxypeptidase Serine-type D-Ala-D-Ala carboxypeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.16.4 3.4.16.4] </span></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=4bl2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bl2 OCA], [https://pdbe.org/4bl2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bl2 RCSB], [https://www.ebi.ac.uk/pdbsum/4bl2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bl2 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=4bl2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bl2 OCA], [http://pdbe.org/4bl2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bl2 RCSB], [http://www.ebi.ac.uk/pdbsum/4bl2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bl2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A0H3JPA5_STAAM A0A0H3JPA5_STAAM] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4bl2" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4bl2" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Serine-type D-Ala-D-Ala carboxypeptidase]] | + | [[Category: Large Structures]] |
| - | [[Category: Hermoso, J A]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Otero, L H]] | + | [[Category: Hermoso JA]] |
| - | [[Category: Rojas-Altuve, A]] | + | [[Category: Otero LH]] |
| - | [[Category: B-lactum antibiotic]] | + | [[Category: Rojas-Altuve A]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Penicillin binding protein]]
| + | |
| Structural highlights
Function
A0A0H3JPA5_STAAM
Publication Abstract from PubMed
Ceftaroline, a recently approved beta-lactam antibiotic for treatment of infections by methicillin-resistant Staphylococcus aureus (MRSA), is able to inhibit penicillin-binding protein 2a (PBP2a) by triggering an allosteric conformational change that leads to the opening of the active site. The opened active site is now vulnerable to inhibition by a second molecule of ceftaroline, an event that impairs cell-wall biosynthesis and leads to bacterial death. The triggering of the allosteric effect takes place by binding of the first antibiotic molecule 60 A away from the active site of PBP2a within the core of the allosteric site. We document, by kinetic studies and by determination of three X-ray structures of the mutant variants of PBP2a that result in resistance to ceftaroline, that the effect of these clinical mutants is the disruption of the allosteric trigger in this important protein in MRSA. This is an unprecedented mechanism for antibiotic resistance.
Disruption of allosteric response as an unprecedented mechanism of resistance to antibiotics.,Fishovitz J, Rojas-Altuve A, Otero LH, Dawley M, Carrasco-Lopez C, Chang M, Hermoso JA, Mobashery S J Am Chem Soc. 2014 Jul 16;136(28):9814-7. doi: 10.1021/ja5030657. Epub 2014 Jul , 2. PMID:24955778[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fishovitz J, Rojas-Altuve A, Otero LH, Dawley M, Carrasco-Lopez C, Chang M, Hermoso JA, Mobashery S. Disruption of allosteric response as an unprecedented mechanism of resistance to antibiotics. J Am Chem Soc. 2014 Jul 16;136(28):9814-7. doi: 10.1021/ja5030657. Epub 2014 Jul , 2. PMID:24955778 doi:http://dx.doi.org/10.1021/ja5030657
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