{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:58:20Z","timestamp":1791316700117,"version":"4.3.1"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2004,5,1]],"date-time":"2004-05-01T00:00:00Z","timestamp":1083369600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2004,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Extensive use of \u03b2-lactam antibiotics has led to the selection of pathogenic streptococci resistant to \u03b2-lactams due to modifications of the penicillin-binding proteins (PBPs). PBP2b from\n            <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n            is a monofunctional (class B) high-molecular-weight PBP catalyzing the transpeptidation between adjacent stem peptides of peptidoglycan. The transpeptidase domain of PBP2b isolated from seven clinical resistant (CR) strains contains 7 to 44 amino acid changes over the sequence of PBP2b from the R6 \u03b2-lactam-sensitive strain. We show that the extracellular soluble domains of recombinant PBP2b proteins (PBP2b*) originating from these CR strains have an in vitro affinity for penicillin G that is reduced by up to 99% from that of the R6 strain. The Thr446Ala mutation is always observed in CR strains and is close to the key conserved motif (S\n            <jats:sub>443<\/jats:sub>\n            SN). The Thr446Ala mutation in R6 PBP2b* displays a 60% reduction in penicillin G affinity in vitro compared to that for the wild-type protein. A recombinant R6 strain expressing the R6 PBP2b Thr446Ala mutation is twofold less sensitive to piperacillin than the parental\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            strain. Analysis of the Thr446Ala mutation in the context of the PBP2b CR sequences revealed that its influence depends upon the presence of other unidentified mutations.\n          <\/jats:p>","DOI":"10.1128\/aac.48.5.1848-1855.2004","type":"journal-article","created":{"date-parts":[[2004,4,22]],"date-time":"2004-04-22T19:58:16Z","timestamp":1082663896000},"page":"1848-1855","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":44,"title":["Biochemical Characterization of\n            <i>Streptococcus pneumoniae<\/i>\n            Penicillin-Binding Protein 2b and Its Implication in \u03b2-Lactam Resistance"],"prefix":"10.1128","volume":"48","author":[{"given":"Estelle","family":"Pagliero","sequence":"first","affiliation":[{"name":"Laboratoire d'Inge\u0301nierie des Macromole\u0301cules"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Chesnel","sequence":"additional","affiliation":[{"name":"Laboratoire d'Inge\u0301nierie des Macromole\u0301cules"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Hopkins","sequence":"additional","affiliation":[{"name":"Laboratoire de Cristallographie Macromole\u0301culaire, Institut de Biologie Structurale Jean-Pierre Ebel (CEA-CNRS UMR 5075-UJF), 38027 Grenoble Cedex 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Croize\u0301","sequence":"additional","affiliation":[{"name":"Service de Bacte\u0301riologie et Virologie, Centre Hospitalier Universitaire, 38043 Grenoble Cedex 09, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otto","family":"Dideberg","sequence":"additional","affiliation":[{"name":"Laboratoire de Cristallographie Macromole\u0301culaire, Institut de Biologie Structurale Jean-Pierre Ebel (CEA-CNRS UMR 5075-UJF), 38027 Grenoble Cedex 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Vernet","sequence":"additional","affiliation":[{"name":"Laboratoire d'Inge\u0301nierie des Macromole\u0301cules"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Marie","family":"Di Guilmi","sequence":"additional","affiliation":[{"name":"Laboratoire d'Inge\u0301nierie des Macromole\u0301cules"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305948200"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.6.1306"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.15.4418-4423.2003"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.5.1650-1658.2003"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.21.5652-5659.1998"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.9.2773-2781.1999"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/abio.2000.4735"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1993.tb01723.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.22.8842"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1989.tb00108.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"7518","DOI":"10.1093\/nar\/17.18.7518","volume":"17","year":"1989","unstructured":"Dowson, C. 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