4CJN

Crystal structure of PBP2a from MRSA in complex with quinazolinone ligand

Summary for 4CJN

• Entry DOI: 10.2210/pdb4cjn/pdb
• Descriptor: PENICILLIN BINDING PROTEIN 2 PRIME, CADMIUM ION, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: hydrolase, immune system, allosteric site
• Biological source: STAPHYLOCOCCUS AUREUS SUBSP. AUREUS MU50
• Total number of polymer chains: 2
• Total formula weight: 148060.63

Authors

Bouley, R.,Otero, L.H.,Rojas-Altuve, A.,Hermoso, J.A. (deposition date: 2013-12-21, release date: 2015-02-11, Last modification date: 2023-12-20)

Primary citation

Bouley, R.,Kumarasiri, M.,Peng, Z.,Otero, L.H.,Song, W.,Suckow, M.A.,Schroeder, V.A.,Wolter, W.R.,Lastochkin, E.,Antunes, N.T.,Pi, H.,Vakulenko, S.,Hermoso, J.A.,Chang, M.,Mobashery, S.
Discovery of Antibiotic (E)-3-(3-Carboxyphenyl)-2-(4-Cyanostyryl)Quinazolin-4(3H)-One.
J.Am.Chem.Soc., 137:1738-, 2015

PubMed Abstract: 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.

PubMed: 25629446
DOI: 10.1021/JACS.5B00056

Experimental method

X-RAY DIFFRACTION (1.947 Å)