{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:04:14Z","timestamp":1789416254132,"version":"build-2803163510"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Human-adapted\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic>Mtb<\/jats:italic>\n                    ) also infects animals and transmits zoonotically, threatening public health. The cell wall glycolipids lipoarabinomannan and lipomannan are essential virulence factors of\n                    <jats:italic>Mtb<\/jats:italic>\n                    . Phosphatidyl-\n                    <jats:italic>myo<\/jats:italic>\n                    -inositol mannosyltransferase PimA catalyzes a key step in their biosynthesis and represents a potential drug target. However, the functional mechanism of\n                    <jats:italic>Mtb<\/jats:italic>\n                    PimA remains incompletely understood. Here, the hydrodynamic diameter of monomeric PimA was measured as 5.1 \u00b1 0.2 nm. The structural model of PimA was predicted using AlphaFold2. Molecular docking was conducted to predict potential binding sites, and site-directed mutagenesis was then performed. Mutations D253A, E274A or E282A dramatically reduced the activity, whereas R196A, K202A or K256A abolished activity entirely. Guanosine diphosphate (GDP) and benzimidazole inhibited PimA by over 50% at 40 \u00b5M and 10 \u00b5M, respectively. PimA transcription increased linearly over time in macrophages, and conditional PimA-silenced mutant rendered\n                    <jats:italic>Mtb<\/jats:italic>\n                    rapidly susceptible to macrophage killing. These results provide a structural and functional framework for the rational design of novel anti-tubercular agents targeting PimA.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1888373","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T04:37:38Z","timestamp":1787114258000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Functional and mechanistic characterization of the phosphatidyl-myo-inositol mannosyltransferase PimA from Mycobacterium tuberculosis: implications for anti-tuberculosis drug development"],"prefix":"10.3389","volume":"16","author":[{"given":"Dafeng","family":"Liu","sequence":"first","affiliation":[{"name":"College of Biological Sciences and Technology, Yili Normal University","place":["Yining, Xinjiang, China"]},{"name":"School of Life Sciences, Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huashui","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinbao","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenshuang","family":"Yao","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"College of Biological Sciences and Technology, Yili Normal University","place":["Yining, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"37741","DOI":"10.1074\/jbc.M110.165407","article-title":"Acceptor substrate discrimination in phosphatidyl-myo-inositol mannoside synthesis","volume":"285","author":"Batt","year":"2010","journal-title":"J. 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