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GpsB is also required for phosphorylation of proteins by the essential StkP(\n                    <jats:italic>Spn<\/jats:italic>\n                    ) Ser\/Thr protein kinase. Here we report three classes of frequently arising chromosomal duplications (\u224821\u2013176 genes) containing\n                    <jats:italic>murZ<\/jats:italic>\n                    (MurZ\u2010family homolog of MurA) or\n                    <jats:italic>murA<\/jats:italic>\n                    that suppress \u0394\n                    <jats:italic>gpsB<\/jats:italic>\n                    or \u0394\n                    <jats:italic>stkP<\/jats:italic>\n                    . These duplications arose from three different repeated sequences and demonstrate the facility of pneumococcus to modulate gene dosage of numerous genes. Overproduction of MurZ or MurA alone or overproduction of MurZ caused by \u0394\n                    <jats:italic>khpAB<\/jats:italic>\n                    mutations suppressed \u0394\n                    <jats:italic>gpsB<\/jats:italic>\n                    or \u0394\n                    <jats:italic>stkP<\/jats:italic>\n                    phenotypes to varying extents. \u0394\n                    <jats:italic>gpsB<\/jats:italic>\n                    and \u0394\n                    <jats:italic>stkP<\/jats:italic>\n                    were also suppressed by MurZ amino\u2010acid changes distant from the active site, including one in commonly studied laboratory strains, and by truncation or deletion of the homolog of IreB(ReoM). Unlike in other Gram\u2010positive bacteria, MurZ is predominant to MurA in pneumococcal cells. However, \u0394\n                    <jats:italic>gpsB<\/jats:italic>\n                    and \u0394\n                    <jats:italic>stkP<\/jats:italic>\n                    were not suppressed by \u0394\n                    <jats:italic>clpCP<\/jats:italic>\n                    , which did not alter MurZ or MurA amounts. These results support a model in which regulation of MurZ and MurA activity, likely by IreB(\n                    <jats:italic>Spn<\/jats:italic>\n                    ), is the only essential requirement for StkP\u2010mediated protein phosphorylation in exponentially growing D39 pneumococcal cells.\n                  <\/jats:p>","DOI":"10.1111\/mmi.15122","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T22:52:55Z","timestamp":1689375175000},"page":"351-383","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Negative regulation of\n                    <scp>MurZ<\/scp>\n                    and\n                    <scp>MurA<\/scp>\n                    underlies the essentiality of\n                    <scp>GpsB<\/scp>\n                    \u2010 and\n                    <scp>StkP<\/scp>\n                    \u2010mediated protein phosphorylation in\n                    <i>Streptococcus pneumoniae<\/i>\n                    <scp>D39<\/scp>"],"prefix":"10.1111","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0849-874X","authenticated-orcid":false,"given":"Ho\u2010Ching Tiffany","family":"Tsui","sequence":"first","affiliation":[{"name":"Department of Biology Indiana University Bloomington  Bloomington Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0943-920X","authenticated-orcid":false,"given":"Merrin","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Biology Indiana University Bloomington  Bloomington Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3176-2129","authenticated-orcid":false,"given":"Jiaqi J.","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Biology Indiana University Bloomington  Bloomington Indiana 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