Structural characterization of glycinamide-RNase-transformylase T from Mycobacterium tuberculosis
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-...
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Taylor & Francis Group
2020-01-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2019.1707716 |
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| author | Cong Chen Zuliang Liu Liguo Liu Jianmin Wang Qi Jin |
| author_facet | Cong Chen Zuliang Liu Liguo Liu Jianmin Wang Qi Jin |
| author_sort | Cong Chen |
| collection | DOAJ |
| description | 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 Å. 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 Å 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. |
| format | Article |
| id | doaj-art-8bf8986a1e444ddfafec322f79ae36f0 |
| institution | OA Journals |
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| language | English |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
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| series | Emerging Microbes and Infections |
| spelling | doaj-art-8bf8986a1e444ddfafec322f79ae36f02025-08-20T02:12:20ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-0191586610.1080/22221751.2019.1707716Structural characterization of glycinamide-RNase-transformylase T from Mycobacterium tuberculosisCong Chen0Zuliang Liu1Liguo Liu2Jianmin Wang3Qi Jin4NHC 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 ChinaNHC 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 ChinaNHC 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 ChinaNHC 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 ChinaNHC 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 ChinaEnzymes 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 Å. 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 Å 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.https://www.tandfonline.com/doi/10.1080/22221751.2019.1707716Mycobacterium tuberculosisglycinamide-RNase-transformylase Tcrystal structurepurine salvage pathwayanti-TB drug development |
| spellingShingle | Cong Chen Zuliang Liu Liguo Liu Jianmin Wang Qi Jin Structural characterization of glycinamide-RNase-transformylase T from Mycobacterium tuberculosis Emerging Microbes and Infections Mycobacterium tuberculosis glycinamide-RNase-transformylase T crystal structure purine salvage pathway anti-TB drug development |
| title | Structural characterization of glycinamide-RNase-transformylase T from Mycobacterium tuberculosis |
| title_full | Structural characterization of glycinamide-RNase-transformylase T from Mycobacterium tuberculosis |
| title_fullStr | Structural characterization of glycinamide-RNase-transformylase T from Mycobacterium tuberculosis |
| title_full_unstemmed | Structural characterization of glycinamide-RNase-transformylase T from Mycobacterium tuberculosis |
| title_short | Structural characterization of glycinamide-RNase-transformylase T from Mycobacterium tuberculosis |
| title_sort | structural characterization of glycinamide rnase transformylase t from mycobacterium tuberculosis |
| topic | Mycobacterium tuberculosis glycinamide-RNase-transformylase T crystal structure purine salvage pathway anti-TB drug development |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2019.1707716 |
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