Mutational analyses of human thymidine kinase 2 reveal key residues in ATP-Mg2+ binding and catalysis

Abstract

Mitochondrial thymidine kinase 2 (TK2) is an essential enzyme for mitochondrial dNTP synthesis in many tissues. Deficiency in TK2 activity causes devastating mitochondrial diseases. Here we investigated several residues involved in substrate binding and catalysis. We showed that mutations of Gln-110 and Glu-133 affected Mg2+ and ATP binding, and thus are crucial for TK2 function. Furthermore, mutations of Gln-110 and Tyr-141 altered the kinetic behavior, suggesting their involvement in substrate binding through conformational changes. Since the 3 D structure of TK2 is still unknown, and thus, the identification of key amino acids for TK2 function may help to explain how TK2 mutations cause mitochondrial diseases.

Keywords

thymidine kinase 2; mutagenesis; substrate binding; ATP; Mg2+ binding; enzyme kinetics

Published in

Nucleosides, Nucleotides and Nucleic Acids
2022, Volume: 41, number: 3, pages: 264-272
Publisher: TAYLOR AND FRANCIS INC

SLU Authors

• Wang, Liya

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

• Eriksson, Staffan

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Biochemistry and Molecular Biology


Publication identifier

DOI: https://doi.org/10.1080/15257770.2021.2001005

Permanent link to this page (URI)

https://res.slu.se/id/publ/116661