8WX0

PNPase of M.tuberculosis with its RNA substrate

Summary for 8WX0

• Entry DOI: 10.2210/pdb8wx0/pdb
• EMDB information: 37896
• Descriptor: Bifunctional guanosine pentaphosphate synthetase/polyribonucleotide nucleotidyltransferase, RNA (24-mer) (3 entities in total)
• Functional Keywords: pnpase, mycobacterium tuberculosis, complex, transferase, transferase-rna complex, transferase/rna
• Biological source: Mycobacterium tuberculosis; More
• Total number of polymer chains: 7
• Total formula weight: 277080.19

Authors

Wang, N.,Sheng, Y.N. (deposition date: 2023-10-27, release date: 2024-07-03)

Primary citation

Wang, N.,Sheng, Y.,Liu, Y.,Guo, Y.,He, J.,Liu, J.
Cryo-EM structures of Mycobacterium tuberculosis polynucleotide phosphorylase suggest a potential mechanism for its RNA substrate degradation.
Arch.Biochem.Biophys., 754:109917-109917, 2024

PubMed Abstract: 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.

PubMed: 38395123
DOI: 10.1016/j.abb.2024.109917

Experimental method

ELECTRON MICROSCOPY (3.7 Å)