View source for 4cpk


==Crystal structure of PBP2a double clinical mutant N146K-E150K from MRSA==
<StructureSection load='4cpk' size='340' side='right'caption='[[4cpk]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4cpk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staam Staam]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CPK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CPK FirstGlance]. <br>
</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>, <scene name='pdbligand=MUR:MURAMIC+ACID'>MUR</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Serine-type_D-Ala-D-Ala_carboxypeptidase Serine-type D-Ala-D-Ala carboxypeptidase], with EC number [https://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=4cpk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cpk OCA], [https://pdbe.org/4cpk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cpk RCSB], [https://www.ebi.ac.uk/pdbsum/4cpk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cpk ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== 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<ref>PMID:24955778</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4cpk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Serine-type D-Ala-D-Ala carboxypeptidase]]
[[Category: Staam]]
[[Category: Hermoso, J A]]
[[Category: Otero, L H]]
[[Category: Rojas-Altuve, A]]
[[Category: Allosteric site]]
[[Category: Hydrolase]]
[[Category: Mrsa]]
[[Category: Penicillin-binding protein]]