{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T12:06:28Z","timestamp":1779105988446,"version":"3.51.4"},"posted":{"date-parts":[[2025,2,1]]},"reference-count":0,"publisher":"Wiley","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Methicillin-resistant Staphylococcus aureus (MRSA) is a major global\nchallenge due to its resistance to \u03b2-lactam antibiotics. This resistance\nstems from the mecA gene, which encodes penicillin-binding protein 2a\n(PBP2a). PBP2a enables bacterial survival by catalyzing peptidoglycan\nsynthesis while exhibiting low affinity for \u03b2-lactams. Its active site\nis shielded by protective loops, adopting a closed conformation that\nlimits drug access. These structural changes are regulated by an\nallosteric site distant from the active site. Given the urgent need for\nnew therapeutic strategies, this review focuses on PBP2a\u2019s\nconformational dynamics and allosteric regulation in \u03b2-lactam\nresistance. Additionally, it explores ligand interactions that influence\nPBP2a inhibition and their potential in restoring antibiotic efficacy.\nUnderstanding these mechanisms will aid the design of adjuvants\ntargeting the allosteric site, offering a promising strategy to enhance\n\u03b2-lactam effectiveness against MRSA.<\/jats:p>","DOI":"10.22541\/au.173840407.75774545\/v1","type":"posted-content","created":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T05:01:24Z","timestamp":1738386084000},"source":"Crossref","is-referenced-by-count":0,"title":["Targeting MRSA penicillin-binding protein 2a: structural insights, allosteric mechanisms, and the potential of adjuvant inhibitors"],"prefix":"10.22541","author":[{"given":"Pedro","family":"Rosado","sequence":"first","affiliation":[{"name":"Universidade de Lisboa Instituto Superior T\u00e9cnico"}]},{"given":"M. Matilde","family":"Marques","sequence":"additional","affiliation":[{"name":"Instituto Superior T\u00e9cnico, Universidade de Lisboa"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4828-4738","authenticated-orcid":false,"given":"Goncalo","family":"Justino","sequence":"additional","affiliation":[{"name":"Instituto Polit\u00e9cnico de Set\u00fabal Escola Superior de Tecnologia do Barreiro"}]}],"member":"311","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.authorea.com\/doi\/pdf\/10.22541\/au.173840407.75774545\/v1","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T11:06:52Z","timestamp":1779102412000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.authorea.com\/doi\/full\/10.22541\/au.173840407.75774545\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,1]]},"references-count":0,"URL":"https:\/\/doi.org\/10.22541\/au.173840407.75774545\/v1","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1016\/j.bcp.2025.117048","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,2,1]]},"subtype":"preprint"}}