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Title-Adenosylmethionine-responsive cystathionine β-synthase modulates sulfur metabolism and redox balance in .
Journal, issue, pagesSci Adv, Vol. 8, Issue 25, Page eabo0097, Year 2022
Publish dateJun 24, 2022
AuthorsParijat Bandyopadhyay / Ishika Pramanick / Rupam Biswas / Sabarinath Ps / Sreesa Sreedharan / Shalini Singh / Raju S Rajmani / Sunil Laxman / Somnath Dutta / Amit Singh /
PubMed AbstractMethionine and cysteine metabolisms are important for the survival and pathogenesis of (). The transsulfuration pathway converts methionine to cysteine and represents an important link between ...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 .
External linksSci Adv / PubMed:35749503 / PubMed Central
MethodsEM (single particle)
Resolution3.6 - 4.25 Å
Structure data

33331

7xnz

EMDB-33331: Cyo-EM model for native cystathionine beta-synthase of Mycobacterium tuberculosis.
PDB-7xnz: Native cystathionine beta-synthase of Mycobacterium tuberculosis.
Method: EM (single particle) / Resolution: 3.6 Å

33348

7xoh

EMDB-33348: Cryo-EM map of cystathionine beta-synthase of Mycobacterium tuberculosis in the presence of S-adenosylmethionine.
PDB-7xoh: Cystathionine beta-synthase of Mycobacterium tuberculosis in the presence of S-adenosylmethionine.
Method: EM (single particle) / Resolution: 3.6 Å

33363

7xoy

EMDB-33363: Cryo-EM map of cystathionine beta-synthase of Mycobacterium tuberculosis in the presence of S-adenosylmethionine and serine.
PDB-7xoy: Cystathionine beta-synthase of Mycobacterium tuberculosis in the presence of S-adenosylmethionine and serine.
Method: EM (single particle) / Resolution: 4.25 Å

Chemicals

ChemComp-PLP:
PYRIDOXAL-5'-PHOSPHATE / Pyridoxal phosphate

ChemComp-PLS:
[3-HYDROXY-2-METHYL-5-PHOSPHONOOXYMETHYL-PYRIDIN-4-YLMETHYL]-SERINE

Source
  • Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria)
  • mycobacterium tuberculosis h37rv (bacteria)
KeywordsLYASE / cystathionine beta-synthase / transsulfuration / S-adenosylmethionine

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