Download MendeleyStructural characterization of glycinamide-RNase-transformylase T fromMycobacterium tuberculosis.
Chen, C., Liu, Z., Liu, L., Wang, J., Jin, Q.(2020) Emerg Microbes Infect 9: 58-66
- PubMed: 31894729
- DOI: https://doi.org/10.1080/22221751.2019.1707716
- Primary Citation of Related Structures:
6KHR - PubMed Abstract:
Enzymes from the purine salvage pathway in Mycobacterium tuberculosis ( Mtb ) have been regarded as an attractive target for the development of anti-bacterial drugs. Although this pathway has not been extensively studied in Mtb , it has been identified as essential for growth and survival. Glycinamide-RNase-transformylase T (PurT) is found only in some specific bacteria including Mtb and utilizes ATP-dependent ligation to catalyze the formylation of 5'-phosphoribosyl-glycinamide (GAR) in the third reaction of the de novo purine salvage pathway. In the study, we determined the crystal structure of Mtb PurT at a resolution of 2.79 Å. In contrast to Pyrococcus horikoshii OT3 PurT (phBCCPPurT), Mtb PurT exhibits an "open" conformation, which results in a broader ATP-binding pocket and thus might facilitate the entry and exit of the cofactor. Additionally, active site superposition with E.coli PurT ( Ec PurT) showed that residues involved in the ATP-binding site in Mtb PurT exhibited structural similarity but had notable difference in the GAR-binding site. The loop 383-389 in Mtb PurT was much shorter and shifted 5.7 Å away from the phosphate of the GAR substrate. The different GAR-binding mode might result in a large conformational change in Mtb PurT, and would provide a possible opportunity for anti-TB drug development.
Organizational Affiliation:
NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. People's Republic of China.
