Published on Jan. 1, 2020 in volume Emerg Microbes Infect 9: 58-66.

PubMed ID: 31894729

DOI: 10.1080/22221751.2019.1707716

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.