{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T09:57:01Z","timestamp":1781690221076,"version":"3.54.5"},"reference-count":109,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research","doi-asserted-by":"crossref","award":["OLP0162"],"award-info":[{"award-number":["OLP0162"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"crossref"}]},{"name":"DBT-Wellcome Trust India","award":["IA\/S\/19\/2\/504\u2009646"],"award-info":[{"award-number":["IA\/S\/19\/2\/504\u2009646"]}]},{"DOI":"10.13039\/501100001843","name":"Anusandhan National Research Foundation","doi-asserted-by":"crossref","award":["SPR\/2023\/000\u2009423"],"award-info":[{"award-number":["SPR\/2023\/000\u2009423"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Centre of Excellence for Anti-Viral and Anti-Bacterial Drug Discovery and Development"},{"name":"Department of Pharmaceuticals, Government of India, New Delhi"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mycobacterium tuberculosis (Mtb) encodes a huge repertoire of toxin\u2013antitoxin (TA) systems, many of which remain uncharacterized. Here, we report the crystal structures of the VapC52 toxin and VapBC52 TA complex at a resolution of 2.6 and 3.2 \u00c5, respectively. We show that VapC52 adopts a unique open dimeric conformation and inhibits mycobacterial growth by cleaving tRNA at the variable or anticodon loop region. Structure reveals that VapB52 adopts a distinct structural architecture and binds VapC52 with a 1:2 stoichiometry, respectively. Interestingly, binding of ssDNA activates VapB52 peptidase domain, resulting in auto-cleavage of VapB52 N-terminal domain which is critical for VapBC complex formation and neutralization. In addition to VapB52, co-expression of several other non-cognate VapB antitoxins abrogates the growth inhibition associated with VapC52 overexpression in Mycobacterium smegmatis (Msm) suggesting crosstalk among VapBC TA systems. Further, we demonstrate that the vapBC52 locus is dispensable for in vitro growth but essential for Mtb intracellular growth in macrophages and guinea pigs. Notably, VapC52 also cleaves mycobacteriophage D29 encoded tRNAs and confers resistance to phage infection in Msm. Taken together, we show that VapBC52 adopts a unique structural architecture, plays role in pathogenesis, and is possibly involved in mycobacterial antiphage defense mechanisms.<\/jats:p>","DOI":"10.1093\/nar\/gkag611","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:45:03Z","timestamp":1780487103000},"source":"Crossref","is-referenced-by-count":0,"title":["Structural and functional characterization of VapBC52 toxin\u2013antitoxin system from\n                    <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1093","volume":"54","author":[{"given":"Manisha","family":"Singh","sequence":"first","affiliation":[{"name":"Centre for Tuberculosis Research, Tuberculosis Research Laboratory, BRIC-Translational Health Science and Technology Institute, Faridabad\u2013Gurugram Expressway , Faridabad, Haryana 121001 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charandeep","family":"Singh","sequence":"additional","affiliation":[{"name":"Structural Biology Laboratory, CSIR-Institute of Microbial Technology , Sector 39A, Chandigarh 160036 ,","place":["India"]},{"name":"Academy of Scientific and Innovative Research (AcSIR) , Ghaziabad 201002 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay V","family":"Nair","sequence":"additional","affiliation":[{"name":"Microbiology and Molecular Biology Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Bhopal , Madhya Pradesh 462066 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Centre for Tuberculosis Research, Tuberculosis Research Laboratory, BRIC-Translational Health Science and Technology Institute, Faridabad\u2013Gurugram Expressway , Faridabad, Haryana 121001 ,","place":["India"]},{"name":"Manipal Academy of Higher Education , Manipal, Karnataka 576104 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Sharma","sequence":"additional","affiliation":[{"name":"Centre for Tuberculosis Research, Tuberculosis Research Laboratory, BRIC-Translational Health Science and Technology Institute, Faridabad\u2013Gurugram Expressway , Faridabad, Haryana 121001 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munmun","family":"Bhasin","sequence":"additional","affiliation":[{"name":"Molecular Biophysics Unit, Indian Institute of Science , Bangalore 560012 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0238-8144","authenticated-orcid":false,"given":"Vikas","family":"Jain","sequence":"additional","affiliation":[{"name":"Laboratory of Antimicrobial Innovation, School of Interwoven Arts and Sciences, Krea University , Sri City, Andhra Pradesh 517646 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2705-3826","authenticated-orcid":false,"given":"Ramandeep","family":"Singh","sequence":"additional","affiliation":[{"name":"Centre for Tuberculosis Research, Tuberculosis Research Laboratory, BRIC-Translational Health Science and Technology Institute, Faridabad\u2013Gurugram Expressway , Faridabad, Haryana 121001 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4500-2133","authenticated-orcid":false,"given":"Krishan Gopal","family":"Thakur","sequence":"additional","affiliation":[{"name":"Structural Biology Laboratory, CSIR-Institute of Microbial Technology , Sector 39A, Chandigarh 160036 ,","place":["India"]},{"name":"Academy of Scientific and Innovative Research (AcSIR) , Ghaziabad 201002 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