{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T12:40:56Z","timestamp":1784896856590,"version":"3.55.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100005847","name":"FHB | Health and Medical Research Fund","doi-asserted-by":"publisher","award":["14130502"],"award-info":[{"award-number":["14130502"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Bacterial \u03b2-lactamases readily inactivate most penicillins and cephalosporins by hydrolyzing and \u201copening\u201d their signature \u03b2-lactam ring. In contrast, carbapenems resist hydrolysis by many serine-based class A, C, and D \u03b2-lactamases due to their unique stereochemical features. To improve the resistance profile of penicillins, we synthesized a modified penicillin molecule, MPC-1, by \u201cgrafting\u201d carbapenem-like stereochemistry onto the penicillin core. Chemical modifications include the\n            <jats:italic>trans<\/jats:italic>\n            conformation of hydrogen atoms at C-5 and C-6 instead of\n            <jats:italic>cis<\/jats:italic>\n            , and a 6-\u03b1 hydroxyethyl moiety to replace the original 6-\u03b2 aminoacyl group. MPC-1 selectively inhibits class C \u03b2-lactamases, such as P99, by forming a nonhydrolyzable acyl adduct, and its inhibitory potency is \u223c2 to 5 times higher than that for clinically used \u03b2-lactamase inhibitors clavulanate and sulbactam. The crystal structure of MPC-1 forming the acyl adduct with P99 reveals a novel binding mode for MPC-1 that resembles carbapenem bound in the active site of class A \u03b2-lactamases. Furthermore, in this novel binding mode, the carboxyl group of MPC-1 blocks the deacylation reaction by occluding the critical catalytic water molecule and renders the acyl adduct nonhydrolyzable. Our results suggest that by incorporating carbapenem-like stereochemistry, the current collection of over 100 penicillins and cephalosporins can be modified into candidate compounds for development of novel \u03b2-lactamase inhibitors.\n          <\/jats:p>","DOI":"10.1128\/aac.01288-17","type":"journal-article","created":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T00:30:26Z","timestamp":1506990626000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["Modified Penicillin Molecule with Carbapenem-Like Stereochemistry Specifically Inhibits Class C \u03b2-Lactamases"],"prefix":"10.1128","volume":"61","author":[{"given":"Xuehua","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Chemistry, Jinan University, Guangzhou, People's Republic of China"},{"name":"The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, People's Republic of China"},{"name":"Department of Applied Biology and Chemical Technology, State Key Laboratory of Chirosciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjiao","family":"He","sequence":"additional","affiliation":[{"name":"Department of Biology and Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen, People\u2019s Republic of China"},{"name":"Department of Applied Biology and Chemical Technology, State Key Laboratory of Chirosciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianfeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Jinan University, Guangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kin-Fai","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Applied Biology and Chemical Technology, State Key Laboratory of Chirosciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, People's Republic of China"},{"name":"Department of Applied Biology and Chemical Technology, State Key Laboratory of Chirosciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, People\u2019s Republic of 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