Mitochondrial deoxyguanosine kinase mutations and mitochondrial DNA depletion syndrome

Sammanfattning

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. 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. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Nyckelord

deoxyguanosine kinase; mutation; DNA precursor; mitochondrial DNA depletion

Publicerad i

FEBS Letters
2003, volym: 554, nummer: 3, sidor: 319-322
Utgivare: ELSEVIER SCIENCE BV

SLU författare

• Eriksson, Staffan

  • Institutionen för molekylär biovetenskap, Sveriges lantbruksuniversitet
    

• Wang, Liya

  • Institutionen för molekylär biovetenskap, Sveriges lantbruksuniversitet
    

UKÄ forskningsämne

Cell- och molekylärbiologi

Publikationens identifierare

• DOI: https://doi.org/10.1016/S0014-5793(03)01181-5

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/1814