{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:06:30Z","timestamp":1753869990259,"version":"3.41.2"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T00:00:00Z","timestamp":1649462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001869","name":"Academia Sinica","doi-asserted-by":"publisher","award":["AS\u2010CFII\u2010108\u2010111"],"award-info":[{"award-number":["AS\u2010CFII\u2010108\u2010111"]}],"id":[{"id":"10.13039\/501100001869","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In <jats:italic>Staphylococcus aureus<\/jats:italic>, vancomycin\u2010resistance\u2010associated response regulator (VraR) is a part of the VraSR two\u2010component system, which is responsible for activating a cell wall\u2010stress stimulon in response to an antibiotic that inhibits cell wall formation. Two VraR\u2010binding sites have been identified: R1 and R2 in the <jats:italic>vraSR<\/jats:italic> operon control region. However, the binding of VraR to a promoter DNA enhancing downstream gene expression remains unclear. VraR contains a conserved N\u2010terminal receiver domain (VraR<jats:sub>N<\/jats:sub>) connected to a C\u2010terminal DNA binding domain (VraR<jats:sub>C<\/jats:sub>) with a flexible linker. Here, we present the crystal structure of VraR<jats:sub>C<\/jats:sub> alone and in complex with R1\u2010DNA in 1.87\u2010 and 2.0\u2010\u00c5 resolution, respectively. VraR<jats:sub>C<\/jats:sub> consisting of four \u03b1\u2010helices forms a dimer when interacting with R1\u2010DNA. In the VraR<jats:sub>C<\/jats:sub>\u2013DNA complex structure, Mg<jats:sup>2+<\/jats:sup> ion is bound to Asp194. Biolayer interferometry experiments revealed that the addition of Mg<jats:sup>2+<\/jats:sup> to VraR<jats:sub>C<\/jats:sub> enhanced its DNA binding affinity by eightfold. In addition, interpretation of NMR titrations between VraR<jats:sub>C<\/jats:sub> with R1\u2010 and R2\u2010DNA revealed the essential residues that might play a crucial role in interacting with DNA of the <jats:italic>vraSR<\/jats:italic> operon. The structural information could help in designing and screening potential therapeutics\/inhibitors to deal with antibiotic\u2010resistant <jats:italic>S. aureus<\/jats:italic> via targeting VraR.<\/jats:p>","DOI":"10.1002\/pro.4286","type":"journal-article","created":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T13:56:49Z","timestamp":1649512609000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Structural insights into <scp>DNA<\/scp> binding domain of vancomycin\u2010resistance\u2010associated response regulator in complex with its promoter <scp>DNA<\/scp> from <i>Staphylococcus aureus<\/i>"],"prefix":"10.1002","volume":"31","author":[{"given":"Jangam Vikram","family":"Kumar","sequence":"first","affiliation":[{"name":"Institute of Biomedical Sciences, Academia Sinica  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tien\u2010Sheng","family":"Tseng","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, National Chung Hsing University  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan\u2010Chao","family":"Lou","sequence":"additional","affiliation":[{"name":"Biomedical Translation Research Center Academia Sinica  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu\u2010Yi","family":"Wei","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Academia Sinica  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsung\u2010Han","family":"Wu","sequence":"additional","affiliation":[{"name":"Genome and Systems Biology Degree Program National Taiwan University and Academia Sinica  Taipei 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