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To address <jats:italic>Mtb<\/jats:italic> drug resistance and the limitations of current vaccines, the characteristics of candidate <jats:italic>Mtb<\/jats:italic> vaccines need to be explored. Here, we report the three-dimensional structure of Rv0315 at 1.70\u2009\u00c5 resolution, a novel immunostimulatory antigen of <jats:italic>Mtb<\/jats:italic> and demonstrate that Rv0315 is an inactive \u03b2-1,3-glucanase of the glycoside hydrolase 16 (GH16) family. Our study further elaborates the molecular basis for the lack of glucan recognition by Rv0315. Rv0315 has a large open groove and this particular topology cannot bind oligosaccharide chains in solution, thus explaining the lack of detectable hydrolytic activity towards its substrate. Additionally, we identified Glu-176, a conserved catalytic residue in GH16 endo-\u03b2-1,3-glucanases, as essential for Rv0315 to induce immunological responses. These results indicate that Rv0315 likely diverged from a broad-specificity ancestral GH16 glucanase and this inactive member of the GH16 family offers new insights into the GH16 glucanase. Together, our findings suggest that an inactive \u03b2-1,3-glucanase in <jats:italic>Mtb<\/jats:italic> drives T-helper 1 (Th1) immune responses, which may help develop more effective vaccines against <jats:italic>Mtb<\/jats:italic> infection.<\/jats:p>","DOI":"10.1038\/srep15073","type":"journal-article","created":{"date-parts":[[2015,10,15]],"date-time":"2015-10-15T13:12:03Z","timestamp":1444914723000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Crystal structural basis for Rv0315, an immunostimulatory antigen and inactive beta-1,3-glucanase of Mycobacterium tuberculosis"],"prefix":"10.1038","volume":"5","author":[{"given":"Wanyu","family":"Dong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhua","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yubei","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhou","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunfeng","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaobo","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huanchun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen F.","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guiqing","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,10,15]]},"reference":[{"key":"BFsrep15073_CR1","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S0966-842X(98)01216-5","volume":"6","author":"NM Parrish","year":"1998","unstructured":"Parrish, N. 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