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Molecular structure of a 5,10-methylenetetrahydrofolate dehydrogenase from the silkworm Bombyx mori.
FEBS Open Bio. 2019 04; 9(4):618-628.FO

Abstract

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.

Authors+Show Affiliations

Department of Bioscience and Biotechnology Kyushu University Graduate School Fukuoka Japan.Institute for Protein Research Osaka University Suita Japan. Present address: Department of Virology Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan.Institute for Protein Research Osaka University Suita Japan.Department of Bioscience and Biotechnology Kyushu University Graduate School Fukuoka Japan.Department of Bioscience and Biotechnology Kyushu University Graduate School Fukuoka Japan.Department of Bioscience and Biotechnology Kyushu University Graduate School Fukuoka Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30984537

Citation

Haque, Mohammad R., et al. "Molecular Structure of a 5,10-methylenetetrahydrofolate Dehydrogenase From the Silkworm Bombyx Mori." FEBS Open Bio, vol. 9, no. 4, 2019, pp. 618-628.
Haque MR, Higashiura A, Nakagawa A, et al. Molecular structure of a 5,10-methylenetetrahydrofolate dehydrogenase from the silkworm Bombyx mori. FEBS Open Bio. 2019;9(4):618-628.
Haque, M. R., Higashiura, A., Nakagawa, A., Hirowatari, A., Furuya, S., & Yamamoto, K. (2019). Molecular structure of a 5,10-methylenetetrahydrofolate dehydrogenase from the silkworm Bombyx mori. FEBS Open Bio, 9(4), 618-628. https://doi.org/10.1002/2211-5463.12595
Haque MR, et al. Molecular Structure of a 5,10-methylenetetrahydrofolate Dehydrogenase From the Silkworm Bombyx Mori. FEBS Open Bio. 2019;9(4):618-628. PubMed PMID: 30984537.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular structure of a 5,10-methylenetetrahydrofolate dehydrogenase from the silkworm Bombyx mori. AU - Haque,Mohammad R, AU - Higashiura,Akifumi, AU - Nakagawa,Atsushi, AU - Hirowatari,Aiko, AU - Furuya,Shigeki, AU - Yamamoto,Kohji, Y1 - 2019/02/26/ PY - 2018/12/16/received PY - 2018/12/27/revised PY - 2019/01/14/accepted PY - 2019/4/16/entrez PY - 2019/4/16/pubmed PY - 2019/11/13/medline KW - 5,10‐methylenetetrahydrofolate dehydrogenase KW - Bombyx mori KW - NADP KW - crystal structure KW - serine SP - 618 EP - 628 JF - FEBS open bio JO - FEBS Open Bio VL - 9 IS - 4 N2 - 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. SN - 2211-5463 UR - https://www.unboundmedicine.com/medline/citation/30984537/Molecular_structure_of_a_510_methylenetetrahydrofolate_dehydrogenase_from_the_silkworm_Bombyx_mori_ L2 - https://doi.org/10.1002/2211-5463.12595 DB - PRIME DP - Unbound Medicine ER -