Frisk, Jun Mei Hu
- Department of Animal Biosciences, Swedish University of Agricultural Sciences
Abstract
Drosophila has been used as an animal model to study pathogenic mechanism of neurological disorders. Thymidylate kinase (TMPK) is an essential enzyme in dTTP synthesis catalyzing the phosphorylation of dTMP to dTDP. Loss of function mutations in the DTYMK gene, coding for TMPK, cause severe microcephaly in human patients. In this study, Drosophila melanogaster TMPK (DmTMPK) was cloned, expressed, purified and characterized. Unlike human TMPK, DmTMPK phosphorylated not only dTMP and dUMP but also dGMP and dIMP although with low efficiency. ATP and dATP are the most efficient phosphate donor but at higher concentration (>1 mM) ATP inhibited DmTMPK activity. Sequence and structural model analysis explain why DmTMPK could phosphorylate purine nucleoside monophosphates. This study has laid a solid foundation for future study of TMPK function in Drosophila.
Keywords
Drosophila melanogaster; thymidylate kinase; TMPK; dGMP phosphorylation; structural modeling
Published in
Nucleosides, Nucleotides and Nucleic Acids
2024, volume: 43, number: 8, pages: 734-742
Publisher: TAYLOR AND FRANCIS INC
SLU Authors
Wang, Liya
- Department of Animal Biosciences, Swedish University of Agricultural Sciences
- Department of Animal Biosciences, Swedish University of Agricultural Sciences
UKÄ Subject classification
Molecular Biology
Neurosciences
Publication identifier
- DOI: https://doi.org/10.1080/15257770.2024.2332410
Permanent link to this page (URI)
https://res.slu.se/id/publ/142343