4cjn: Difference between revisions
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==Crystal structure of PBP2a from MRSA in complex with quinazolinone ligand== | |||
<StructureSection load='4cjn' size='340' side='right'caption='[[4cjn]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4cjn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_Mu50 Staphylococcus aureus subsp. aureus Mu50]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CJN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CJN FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.947Å</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>, <scene name='pdbligand=QNZ:(E)-3-(2-(4-CYANOSTYRYL)-4-OXOQUINAZOLIN-3(4H)-YL)BENZOIC+ACID'>QNZ</scene></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=4cjn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cjn OCA], [https://pdbe.org/4cjn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cjn RCSB], [https://www.ebi.ac.uk/pdbsum/4cjn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cjn ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A0J9X1X5_STAAM A0A0J9X1X5_STAAM] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In the face of the clinical challenge posed by resistant bacteria, the present needs for novel classes of antibiotics are genuine. In silico docking and screening, followed by chemical synthesis of a library of quinazolinones, led to the discovery of (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one (compound 2) as an antibiotic effective in vivo against methicillin-resistant Staphylococcus aureus (MRSA). This antibiotic impairs cell-wall biosynthesis as documented by functional assays, showing binding of 2 to penicillin-binding protein (PBP) 2a. We document that the antibiotic also inhibits PBP1 of S. aureus, indicating a broad targeting of structurally similar PBPs by this antibiotic. This class of antibiotics holds promise in fighting MRSA infections. | |||
Discovery of Antibiotic (E)-3-(3-Carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one.,Bouley R, Kumarasiri M, Peng Z, Otero LH, Song W, Suckow MA, Schroeder VA, Wolter WR, Lastochkin E, Antunes NT, Pi H, Vakulenko S, Hermoso JA, Chang M, Mobashery S J Am Chem Soc. 2015 Feb 11;137(5):1738-41. doi: 10.1021/jacs.5b00056. Epub 2015, Feb 2. PMID:25629446<ref>PMID:25629446</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4cjn" 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: Staphylococcus aureus subsp. aureus Mu50]] | |||
[[Category: Bouley R]] | |||
[[Category: Hermoso JA]] | |||
[[Category: Otero LH]] | |||
[[Category: Rojas-Altuve A]] | |||
