Mitochondrial deoxyguanosine kinase mutations and mitochondrial DNA depletion syndrome

FEBS Letters

Eriksson, Staffan¹  Wang, Liya¹ 

[1] Department of Molecular Biosciences, Section of Veterinary Medical Biochemistry, SLU, The Biomedical Centre, P.O. Box 575, SE-751 23 Uppsala, Sweden

关键词: Deoxyguanosine kinase;    Mutation;    DNA precursor;    Mitochondrial DNA depletion;    dGK;    deoxyguanosine kinase;    TK2;    thymidine kinase 2;    dGuo;    deoxyguanosine;    dAdo;    deoxyadenosine;    mtDNA;    mitochondrial DNA;    MDS;    mitochondrial DNA depletion syndrome;   

DOI  :  10.1016/S0014-5793(03)01181-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Mitochondrial deoxyguanosine kinase (dGK) catalyzes the initial phosphorylation of purine deoxynucleosides. Mutations in the dGK gene leading to deficiency in dGK activity is one of the causes of severe mitochondrial DNA depletion diseases. We used site-directed mutagenesis to introduce the clinically observed genetic alterations in the dGK gene and characterized the recombinant enzymes. The R142K enzyme had very low activity with deoxyguanosine and no activity with deoxyadenosine. The E227K mutant enzyme had unchanged K _m values for all its substrates but very low V _max values. C-terminal truncated dGK proteins were inactive. These results may help to define the role of dGK in mitochondrial DNA (mtDNA) precursor synthesis.

【 授权许可】

Unknown