Molecular structure of a 5,10‐methylenetetrahydrofolate dehydrogenase from the silkworm Bombyx mori
The enzyme 5,10‐methylenetetrahydrofolate dehydrogenase (MTHFD) is essential for the production of certain amino acids (glycine, serine, and methionine) and nucleic acids (thymidylate and purine). Here, we identified a cDNA encoding this enzyme from the silkworm Bombyx mori. The recombinant B. mori...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-04-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.12595 |
| _version_ | 1797821927457292288 |
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| author | Mohammad R. Haque Akifumi Higashiura Atsushi Nakagawa Aiko Hirowatari Shigeki Furuya Kohji Yamamoto |
| author_facet | Mohammad R. Haque Akifumi Higashiura Atsushi Nakagawa Aiko Hirowatari Shigeki Furuya Kohji Yamamoto |
| author_sort | Mohammad R. Haque |
| collection | DOAJ |
| description | The enzyme 5,10‐methylenetetrahydrofolate dehydrogenase (MTHFD) is essential for the production of certain amino acids (glycine, serine, and methionine) and nucleic acids (thymidylate and purine). Here, we identified a cDNA encoding this enzyme from the silkworm Bombyx mori. The recombinant B. mori MTHFD (bmMTHFD) expressed in Escherichia coli recognized 5,10‐methylenetetrahydrofolate and 5,10‐methenyltetrahydrofolate as substrate in the presence of NADP+ as well as NAD+. The bmMTHFD structure was determined at a resolution of 1.75 Å by X‐ray crystallography. Site‐directed mutagenesis indicated that the amino acid residue Tyr49 contributed to its catalytic activity. Our findings provide insight into the mechanism underlying the activity of MTHFD from B. mori and potentially other insects and may therefore facilitate the development of inhibitors specific to MTHFD as insecticides. |
| first_indexed | 2024-03-13T09:59:54Z |
| format | Article |
| id | doaj.art-920793bc05ea4f97ba18d5039c418688 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-03-13T09:59:54Z |
| publishDate | 2019-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-920793bc05ea4f97ba18d5039c4186882023-05-23T06:46:21ZengWileyFEBS Open Bio2211-54632019-04-019461862810.1002/2211-5463.12595Molecular structure of a 5,10‐methylenetetrahydrofolate dehydrogenase from the silkworm Bombyx moriMohammad R. Haque0Akifumi Higashiura1Atsushi Nakagawa2Aiko Hirowatari3Shigeki Furuya4Kohji Yamamoto5Department of Bioscience and Biotechnology Kyushu University Graduate School Fukuoka JapanInstitute for Protein Research Osaka University Suita JapanInstitute for Protein Research Osaka University Suita JapanDepartment of Bioscience and Biotechnology Kyushu University Graduate School Fukuoka JapanDepartment of Bioscience and Biotechnology Kyushu University Graduate School Fukuoka JapanDepartment of Bioscience and Biotechnology Kyushu University Graduate School Fukuoka JapanThe enzyme 5,10‐methylenetetrahydrofolate dehydrogenase (MTHFD) is essential for the production of certain amino acids (glycine, serine, and methionine) and nucleic acids (thymidylate and purine). Here, we identified a cDNA encoding this enzyme from the silkworm Bombyx mori. The recombinant B. mori MTHFD (bmMTHFD) expressed in Escherichia coli recognized 5,10‐methylenetetrahydrofolate and 5,10‐methenyltetrahydrofolate as substrate in the presence of NADP+ as well as NAD+. The bmMTHFD structure was determined at a resolution of 1.75 Å by X‐ray crystallography. Site‐directed mutagenesis indicated that the amino acid residue Tyr49 contributed to its catalytic activity. Our findings provide insight into the mechanism underlying the activity of MTHFD from B. mori and potentially other insects and may therefore facilitate the development of inhibitors specific to MTHFD as insecticides.https://doi.org/10.1002/2211-5463.125955,10‐methylenetetrahydrofolate dehydrogenaseBombyx moricrystal structureNADPserine |
| spellingShingle | Mohammad R. Haque Akifumi Higashiura Atsushi Nakagawa Aiko Hirowatari Shigeki Furuya Kohji Yamamoto Molecular structure of a 5,10‐methylenetetrahydrofolate dehydrogenase from the silkworm Bombyx mori FEBS Open Bio 5,10‐methylenetetrahydrofolate dehydrogenase Bombyx mori crystal structure NADP serine |
| title | Molecular structure of a 5,10‐methylenetetrahydrofolate dehydrogenase from the silkworm Bombyx mori |
| title_full | Molecular structure of a 5,10‐methylenetetrahydrofolate dehydrogenase from the silkworm Bombyx mori |
| title_fullStr | Molecular structure of a 5,10‐methylenetetrahydrofolate dehydrogenase from the silkworm Bombyx mori |
| title_full_unstemmed | Molecular structure of a 5,10‐methylenetetrahydrofolate dehydrogenase from the silkworm Bombyx mori |
| title_short | Molecular structure of a 5,10‐methylenetetrahydrofolate dehydrogenase from the silkworm Bombyx mori |
| title_sort | molecular structure of a 5 10 methylenetetrahydrofolate dehydrogenase from the silkworm bombyx mori |
| topic | 5,10‐methylenetetrahydrofolate dehydrogenase Bombyx mori crystal structure NADP serine |
| url | https://doi.org/10.1002/2211-5463.12595 |
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