S-Adenosylmethionine-responsive cystathionine ß-synthase modulates sulfur metabolism and redox balance in Mycobacterium tuberculosis.
Sci Adv
; 8(25): eabo0097, 2022 06 24.
Article
em En
| MEDLINE
| ID: mdl-35749503
ABSTRACT
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 ß-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cistationina beta-Sintase
/
Mycobacterium tuberculosis
Limite:
Animals
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Índia