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Publication Abstract from PubMed

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 MtbPurT at a resolution of 2.79 A. In contrast to Pyrococcus horikoshii OT3 PurT (phBCCPPurT), MtbPurT 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 (EcPurT) showed that residues involved in the ATP-binding site in MtbPurT exhibited structural similarity but had notable difference in the GAR-binding site. The loop 383-389 in MtbPurT was much shorter and shifted 5.7 A away from the phosphate of the GAR substrate. The different GAR-binding mode might result in a large conformational change in MtbPurT, and would provide a possible opportunity for anti-TB drug development.

Structural characterization of glycinamide-RNase-transformylase T from Mycobacterium tuberculosis.,Chen C, Liu Z, Liu L, Wang J, Jin Q Emerg Microbes Infect. 2020 Jan 2;9(1):58-66. doi: 10.1080/22221751.2019.1707716. , eCollection 2020. PMID:31894729^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.