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Mitochondrial deoxyguanosine kinase mutations and mitochondrial DNA depletion syndrome
Author(s) -
Wang Liya,
Eriksson Staffan
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01181-5
Subject(s) - deoxyguanosine , mitochondrial dna , microbiology and biotechnology , biochemistry , mutagenesis , biology , mutant , enzyme , mutation , mitochondrion , deoxyadenosine , gene , dna , chemistry
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.