TitleS-Adenosylmethionine-responsive cystathionine β-synthase modulates sulfur metabolism and redox balance in Mycobacterium tuberculosis .
Publication TypeJournal Article
Year of Publication2022
AuthorsBandyopadhyay P, Pramanick I, Biswas R, Ps S, Sreedharan S, Singh S, Rajmani RS, Laxman S, Dutta S, Singh A
JournalSci Adv
Date Published2022 Jun 24
KeywordsAnimals, Cryoelectron Microscopy, Cystathionine beta-Synthase, Cysteine, Methionine, Mice, Mycobacterium tuberculosis, Oxidation-Reduction, Pyridoxal Phosphate, S-Adenosylmethionine, Sulfur

Methionine and cysteine metabolisms are important for the survival and pathogenesis of (). The transsulfuration pathway converts methionine to cysteine and represents an important link between antioxidant and methylation metabolism in diverse organisms. Using a combination of biochemistry and cryo-electron microscopy, we characterized the first enzyme of the transsulfuration pathway, cystathionine β-synthase (Cbs) in . We demonstrated that Cbs is a heme-less, pyridoxal-5'-phosphate-containing enzyme, allosterically activated by -adenosylmethionine (SAM). The atomic model of Cbs in its native and SAM-bound conformations revealed a unique mode of SAM-dependent allosteric activation. Further, SAM stabilized Cbs by sterically occluding proteasomal degradation, which was crucial for supporting methionine and redox metabolism in . Genetic deficiency of Cbs reduced survival upon homocysteine overload in vitro, inside macrophages, and in mice coinfected with HIV. Thus, the Cbs-SAM axis constitutes an important mechanism of coordinating sulfur metabolism in .

Alternate JournalSci Adv
PubMed ID35749503
PubMed Central IDPMC9232105
Grant List / WT_ / Wellcome Trust / United Kingdom
IA/S/16/2/502700 / WTDBT_ / DBT-Wellcome Trust India Alliance / India