Molecular characterization of Drosophila melanogaster thymidylate kinase

被引:0
|
作者
Frisk, Junmei Hu [1 ]
Wang, Liya [1 ]
机构
[1] Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden
来源
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS | 2024年 / 43卷 / 08期
关键词
Drosophila melanogaster; thymidylate kinase; TMPK; dGMP phosphorylation; structural modeling; EFFICIENT PHOSPHORYLATION; DIMERIZATION; DGMP;
D O I
10.1080/15257770.2024.2332410
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:734 / 742
页数:9
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