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-Structure paper
タイトル | -Adenosylmethionine-responsive cystathionine β-synthase modulates sulfur metabolism and redox balance in . |
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ジャーナル・号・ページ | Sci Adv, Vol. 8, Issue 25, Page eabo0097, Year 2022 |
掲載日 | 2022年6月24日 |
著者 | Parijat Bandyopadhyay / Ishika Pramanick / Rupam Biswas / Sabarinath Ps / Sreesa Sreedharan / Shalini Singh / Raju S Rajmani / Sunil Laxman / Somnath Dutta / Amit Singh / |
PubMed 要旨 | 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 ...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 . |
リンク | Sci Adv / PubMed:35749503 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.6 - 4.25 Å |
構造データ | EMDB-33331: Cyo-EM model for native cystathionine beta-synthase of Mycobacterium tuberculosis. EMDB-33348: Cryo-EM map of cystathionine beta-synthase of Mycobacterium tuberculosis in the presence of S-adenosylmethionine. EMDB-33363: Cryo-EM map of cystathionine beta-synthase of Mycobacterium tuberculosis in the presence of S-adenosylmethionine and serine. |
化合物 | ChemComp-PLP: ChemComp-PLS: |
由来 |
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キーワード | LYASE / cystathionine beta-synthase / transsulfuration / S-adenosylmethionine |