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Using a combination of biochemistry and cryo\u2013electron microscopy, we characterized the first enzyme of the transsulfuration pathway, cystathionine \u03b2-synthase (\n                    <jats:italic>Mtb<\/jats:italic>\n                    Cbs) in\n                    <jats:italic>Mtb<\/jats:italic>\n                    . We demonstrated that\n                    <jats:italic>Mtb<\/jats:italic>\n                    Cbs is a heme-less, pyridoxal-5\u2032-phosphate\u2013containing enzyme, allosterically activated by\n                    <jats:italic>S<\/jats:italic>\n                    -adenosylmethionine (SAM). The atomic model of\n                    <jats:italic>Mtb<\/jats:italic>\n                    Cbs in its native and SAM-bound conformations revealed a unique mode of SAM-dependent allosteric activation. Further, SAM stabilized\n                    <jats:italic>Mtb<\/jats:italic>\n                    Cbs by sterically occluding proteasomal degradation, which was crucial for supporting methionine and redox metabolism in\n                    <jats:italic>Mtb<\/jats:italic>\n                    . Genetic deficiency of\n                    <jats:italic>Mtb<\/jats:italic>\n                    Cbs reduced\n                    <jats:italic>Mtb<\/jats:italic>\n                    survival upon homocysteine overload in vitro, inside macrophages, and in mice coinfected with HIV. Thus, the\n                    <jats:italic>Mtb<\/jats:italic>\n                    Cbs-SAM axis constitutes an important mechanism of coordinating sulfur metabolism in\n                    <jats:italic>Mtb<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1126\/sciadv.abo0097","type":"journal-article","created":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T13:58:19Z","timestamp":1656079099000},"source":"Crossref","is-referenced-by-count":35,"title":["<i>S<\/i>\n                    -Adenosylmethionine\u2013responsive cystathionine \u03b2-synthase modulates sulfur metabolism and redox balance in\n                    <i>Mycobacterium<\/i>\n                    <i>tuberculosis<\/i>"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9666-7445","authenticated-orcid":true,"given":"Parijat","family":"Bandyopadhyay","sequence":"first","affiliation":[{"name":"Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka 560012, India."},{"name":"Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, Karnataka 560012, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5441-9670","authenticated-orcid":true,"given":"Ishika","family":"Pramanick","sequence":"additional","affiliation":[{"name":"Molecular Biophysics Unit, Indian Institute of Science, Bangalore, Karnataka 560012, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupam","family":"Biswas","sequence":"additional","affiliation":[{"name":"Molecular Biophysics Unit, Indian Institute of Science, Bangalore, Karnataka 560012, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3146-0184","authenticated-orcid":true,"given":"Sabarinath","family":"PS","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Science and Regenerative Medicine, Bangalore, Karnataka 560065, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreesa","family":"Sreedharan","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Science and Regenerative Medicine, Bangalore, Karnataka 560065, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5564-3466","authenticated-orcid":true,"given":"Shalini","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka 560012, India."},{"name":"Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, Karnataka 560012, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju S.","family":"Rajmani","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, Karnataka 560012, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0861-5080","authenticated-orcid":true,"given":"Sunil","family":"Laxman","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Science and Regenerative Medicine, Bangalore, Karnataka 560065, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3181-0108","authenticated-orcid":true,"given":"Somnath","family":"Dutta","sequence":"additional","affiliation":[{"name":"Molecular Biophysics Unit, Indian Institute of Science, Bangalore, Karnataka 560012, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6761-1664","authenticated-orcid":true,"given":"Amit","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka 560012, India."},{"name":"Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, Karnataka 560012, India."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(01)02238-7"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2012.00331.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"crossref","first-page":"a021121","DOI":"10.1101\/cshperspect.a021121","article-title":"Mycobacterium tuberculosis metabolism","volume":"5","author":"Warner D. 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