{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:21:38Z","timestamp":1791094898665,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2002,1,18]],"date-time":"2002-01-18T00:00:00Z","timestamp":1011312000000},"content-version":"vor","delay-in-days":688,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2000,3]]},"abstract":"<jats:p>In <jats:italic>Streptococcus pneumoniae<\/jats:italic>, the first four genes of the capsule locus (cpsA to cpsD) are common to most serotypes. By analysis of various in\u2010frame deletion and site\u2010directed mutants, the function of their gene products in capsular polysaccharide (CPS) biosynthesis was investigated. We found that while CpsB, C and D are essential for encapsulation, CpsA is not. CpsC and CpsD have similarity to the amino\u2010terminal and carboxy\u2010terminal regions, respectively, of the autophosphorylating protein\u2010tyrosine kinase Wzc from <jats:italic>Escherichia coli<\/jats:italic>. Alignment of CpsD with Wzc and other related proteins identified conserved Walker A and B sequence motifs and a tyrosine rich domain close to the carboxy\u2010terminus. We have shown that CpsD is also an autophosphorylating protein\u2010tyrosine kinase and that point mutations in cpsD affecting either the ATP\u2010binding domain (Walker A motif) or the carboxy\u2010terminal [YGX]<jats:sub>4<\/jats:sub> repeat domain eliminated tyrosine phosphorylation of CpsD. We describe, for the first time, the phenotypic impact of these two mutations on polysaccharide production and show that they affect CPS production differently. Whereas a mutation in the Walker A motif resulted in loss of encapsulation, mutation of the tyrosines in the [YGX]<jats:sub>4<\/jats:sub> repeat domain resulted in an apparent increase in encapsulation and a mucoid phenotype. These data suggest that autophosphorylation of CpsD at tyrosine attenuates its activity and reduces the level of encapsulation. Additionally, we demonstrated that CpsC is required for CpsD tyrosine phosphorylation and that CpsB influences dephosphorylation of CpsD. These results are consistent with CpsD tyrosine phosphorylation acting to negatively regulate CPS production. This has implications for the function of CpsC\/CpsD homologues in both Gram\u2010positive and Gram\u2010negative bacteria and provides a mechanism to explain regulation of CPS production during pathogenesis.<\/jats:p>","DOI":"10.1046\/j.1365-2958.2000.01808.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T11:29:44Z","timestamp":1047468584000},"page":"1431-1442","source":"Crossref","is-referenced-by-count":180,"title":["Tyrosine phosphorylation of CpsD negatively regulates capsular polysaccharide biosynthesis in <i>Streptococcus pneumoniae<\/i>"],"prefix":"10.1111","volume":"35","author":[{"given":"Judy K.","family":"Morona","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Paton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Morona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,1,18]]},"reference":[{"key":"e_1_2_6_2_1","volume-title":"Cumitech 8.","author":"Anhalt J.P.","year":"1978"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.2.449"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/3.Supplement_1.S1"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.54.1.73"},{"key":"e_1_2_6_6_1","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1128\/iai.57.7.2037-2042.1989","article-title":"Reduced virulence of a defined pneumolysin\u2010negative mutant of Streptococcus pneumoniae","volume":"57","author":"Berry A.M.","year":"1989","journal-title":"Infect Immun"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1995.tb02361.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.63.3.757-761.1995"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00197a001"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00111-8"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01277.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1997.tb10300.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.21.7045-7055.1993"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13477"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/9781555818319.ch15"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(97)00554-4"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.62.12.5384-5396.1994"},{"key":"e_1_2_6_18_1","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1128\/jcm.33.10.2759-2762.1995","article-title":"Six newly recognised types of Streptococcus pneumoniae","volume":"33","author":"Henrichsen J. 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