{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:54:54Z","timestamp":1791194094898,"version":"4.1.0"},"reference-count":24,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2012,3,28]],"date-time":"2012-03-28T00:00:00Z","timestamp":1332892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2012,3,28]],"date-time":"2012-03-28T00:00:00Z","timestamp":1332892800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Microbial Drug Resistance"],"published-print":{"date-parts":[[2012,6,1]]},"abstract":"<jats:p>\n                    Penicillin-binding protein 2x (PBP2x) mutations that occur during the selection with beta-lactams are located within the central penicillin-binding\/transpeptidase (TP) domain, and are believed to mediate resistance by interfering with the formation of a covalent complex of the active site serine with the antibiotic. We now investigated the effect of two point mutations found in two independently obtained laboratory mutants that are located at the surface of the TP domain with their side chains facing outside (G422D respectively R426C). They have no significant effect on resistance to cefotaxime\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    or on binding to Bocillin\u2122FL to the active site\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    using purified PBP2x derivatives, thus apparently do not affect the active site directly. In contrast,\n                    <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                    modeling revealed that they affect van der Waal's interactions with the PASTA1 (PBP and serine\/threonine kinase associated) domain of the C-terminal extension and a noncovalent cefuroxime molecule found in the X-ray structure of an acylated PBP2x, suggesting some effect of the mutations on the interaction of the TP domain with PASTA1 and\/or with the antibiotic associated with PASTA1. The effect of the PASTA domains on covalent binding of PBP2x to Bocillin FL was then investigated using a series of soluble truncated PBP2x derivatives. Deletion of 127 C-terminal residues, that is, of both PASTA domains, decreased binding dramatically by \u223c90%. Surprisingly, deletion of only 40 amino acids resulted in the same phenotype, whereas the absence of 30 amino acids affected binding marginally by 10%, documenting a crucial role of the C-terminal domain for beta-lactam binding.\n                  <\/jats:p>","DOI":"10.1089\/mdr.2012.0022","type":"journal-article","created":{"date-parts":[[2012,3,28]],"date-time":"2012-03-28T15:31:19Z","timestamp":1332948679000},"page":"314-321","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":38,"title":["Mutations in\n                    <i>Streptococcus pneumoniae<\/i>\n                    Penicillin-Binding Protein 2x: Importance of the C-Terminal Penicillin-Binding Protein and Serine\/Threonine Kinase-Associated Domains for Beta-Lactam Binding"],"prefix":"10.1177","volume":"18","author":[{"given":"Patrick","family":"Maurer","sequence":"first","affiliation":[{"name":"University of Kaiserslautern","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katya","family":"Todorova","sequence":"additional","affiliation":[{"name":"University of Kaiserslautern","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Sauerbier","sequence":"additional","affiliation":[{"name":"University of Kaiserslautern","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regine","family":"Hakenbeck","sequence":"additional","affiliation":[{"name":"University of Kaiserslautern","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2012,3,28]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2004.06.060"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/1522-2683()22:5<960::AID-ELPS960>3.0.CO;2-9"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.66.4.702-738.2002"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.3740"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/elps.1150181505"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.12.2"},{"key":"e_1_3_3_8_2","first-page":"755","article-title":"Interaction of non-lytic \u03b2-lactams with penicillin-binding proteins in Streptococcus pneumoniae","volume":"133","author":"Hakenbeck R.","year":"1987","unstructured":"Hakenbeck R., , Tornette S., , Adkinson N.F. 1987. Interaction of non-lytic \u03b2-lactams with penicillin-binding proteins in Streptococcus pneumoniae. J. Gen. Microbiol., 133:755\u2013760.","journal-title":"J. Gen. Microbiol."},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.15.7351"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(89)90358-2"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3002(60)90205-5"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1987.tb01942.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.173.21.6986-6990.1991"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.12.016"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.5.1959-1968.2006"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.12.058"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002182"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0396-284"},{"key":"e_1_3_3_19_2","volume-title":"Molecular Cloning: A Laboratory Manual","author":"Sambrook J.","year":"1989","unstructured":"Sambrook J., , Fritsch E.F., , Maniatis T. 1989. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press: Plainview, New York."},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2008.00105.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.08.039"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.54.4.1133"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(02)02164-3"},{"key":"e_1_3_3_24_2","first-page":"211","article-title":"The ciaR\/ciaH regulatory network of Streptococcus pneumoniae","volume":"4","author":"Z\u00e4hner D.","year":"2002","unstructured":"Z\u00e4hner D., , Kaminski K., , van der Linden M., , Mascher T., , Merai M., , Hakenbeck R. 2002. The ciaR\/ciaH regulatory network of Streptococcus pneumoniae. J. Mol. Microbiol. Biotechnol., 4:211\u2013216.","journal-title":"J. Mol. Microbiol. 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