7xnz

Publication Abstract from PubMed

Methionine and cysteine metabolisms are important for the survival and pathogenesis of Mycobacterium tuberculosis (Mtb). 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 beta-synthase (MtbCbs) in Mtb. We demonstrated that MtbCbs is a heme-less, pyridoxal-5'-phosphate-containing enzyme, allosterically activated by S-adenosylmethionine (SAM). The atomic model of MtbCbs in its native and SAM-bound conformations revealed a unique mode of SAM-dependent allosteric activation. Further, SAM stabilized MtbCbs by sterically occluding proteasomal degradation, which was crucial for supporting methionine and redox metabolism in Mtb. Genetic deficiency of MtbCbs reduced Mtb survival upon homocysteine overload in vitro, inside macrophages, and in mice coinfected with HIV. Thus, the MtbCbs-SAM axis constitutes an important mechanism of coordinating sulfur metabolism in Mtb.

S-Adenosylmethionine-responsive cystathionine beta-synthase modulates sulfur metabolism and redox balance in Mycobacterium tuberculosis.,Bandyopadhyay P, Pramanick I, Biswas R, Ps S, Sreedharan S, Singh S, Rajmani RS, Laxman S, Dutta S, Singh A Sci Adv. 2022 Jun 24;8(25):eabo0097. doi: 10.1126/sciadv.abo0097. Epub 2022 Jun , 24. PMID:35749503^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.