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-Structure paper
タイトル | Cryo-EM structures of Mycobacterium tuberculosis polynucleotide phosphorylase suggest a potential mechanism for its RNA substrate degradation. |
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ジャーナル・号・ページ | Arch Biochem Biophys, Vol. 754, Page 109917, Year 2024 |
掲載日 | 2024年2月22日 |
![]() | Na Wang / Yanan Sheng / Yutong Liu / Yaoting Guo / Jun He / Jinsong Liu / ![]() |
PubMed 要旨 | As one of the oldest infectious diseases in the world, tuberculosis (TB) is the second most deadly infectious disease after COVID-19. Tuberculosis is caused by Mycobacterium tuberculosis (Mtb), which ...As one of the oldest infectious diseases in the world, tuberculosis (TB) is the second most deadly infectious disease after COVID-19. Tuberculosis is caused by Mycobacterium tuberculosis (Mtb), which can attack various organs of the human body. Up to now, drug-resistant TB continues to be a public health threat. Pyrazinamide (PZA) is regarded as a sterilizing drug in the treatment of TB due to its distinct ability to target Mtb persisters. Previously we demonstrated that a D67N mutation in Mycobacterium tuberculosis polynucleotide phosphorylase (MtbPNPase, Rv2783c) confers resistance to PZA and Rv2783c is a potential target for PZA, but the mechanism leading to PZA resistance remains unclear. To gain further insight into the MtbPNPase, we determined the cryo-EM structures of apo Rv2783c, its mutant form and its complex with RNA. Our studies revealed the Rv2783c structure at atomic resolution and identified its enzymatic functional groups essential for its phosphorylase activities. We also investigated the molecular mechanisms underlying the resistance to PZA conferred by the mutation. Our research findings provide structural and functional insights enabling the development of new anti-tuberculosis drugs. |
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手法 | EM (単粒子) |
解像度 | 3.12 - 4.0 Å |
構造データ | EMDB-37895, PDB-8wwp: EMDB-37896, PDB-8wx0: EMDB-37905, PDB-8wxf: |
由来 |
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![]() | TRANSFERASE / polynucleotide phosphorylase / Mycobacterium tuberculosis / RNA degradation / TRANSFERASE/RNA / PNPase / complex / TRANSFERASE-RNA complex |