7XOH

Cystathionine beta-synthase of Mycobacterium tuberculosis in the presence of S-adenosylmethionine.

Summary for 7XOH

• Entry DOI: 10.2210/pdb7xoh/pdb
• EMDB information: 33348
• Descriptor: Putative cystathionine beta-synthase Rv1077, PYRIDOXAL-5'-PHOSPHATE (2 entities in total)
• Functional Keywords: cystathionine beta-synthase, transsulfuration, s-adenosylmethionine, lyase
• Biological source: Mycobacterium tuberculosis H37Rv
• Total number of polymer chains: 4
• Total formula weight: 202127.96

Authors

Bandyopadhyay, P.,Pramanick, I.,Biswas, R.,Sabarinath, P.S.,Sreedharan, S.,Singh, S.,Rajmani, R.,Laxman, S.,Dutta, S.,Singh, A. (deposition date: 2022-05-01, release date: 2022-05-25, Last modification date: 2022-12-07)

Primary citation

Bandyopadhyay, P.,Pramanick, I.,Biswas, R.,Ps, S.,Sreedharan, S.,Singh, S.,Rajmani, R.S.,Laxman, S.,Dutta, S.,Singh, A.
S-Adenosylmethionine-responsive cystathionine beta-synthase modulates sulfur metabolism and redox balance in Mycobacterium tuberculosis.
Sci Adv, 8:eabo0097-eabo0097, 2022

PubMed Abstract: 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 .

PubMed: 35749503
DOI: 10.1126/sciadv.abo0097

Experimental method

ELECTRON MICROSCOPY (3.6 Å)