Wang, Liya and Eriksson, Staffan
(2022).
Mutational analyses of human thymidine kinase 2 reveal key residues in ATP-Mg2+ binding and catalysis.
Nucleosides, Nucleotides and Nucleic Acids. 41
:3
, 264-272
[Research article]
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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.
| Authors/Creators: | Wang, Liya and Eriksson, Staffan | ||||||
|---|---|---|---|---|---|---|---|
| Title: | Mutational analyses of human thymidine kinase 2 reveal key residues in ATP-Mg2+ binding and catalysis | ||||||
| Series Name/Journal: | Nucleosides, Nucleotides and Nucleic Acids | ||||||
| Year of publishing : | 2022 | ||||||
| Volume: | 41 | ||||||
| Number: | 3 | ||||||
| Page range: | 264-272 | ||||||
| Number of Pages: | 9 | ||||||
| Publisher: | TAYLOR AND FRANCIS INC | ||||||
| ISSN: | 1525-7770 | ||||||
| Language: | English | ||||||
| Publication Type: | Research article | ||||||
| Article category: | Scientific peer reviewed | ||||||
| Version: | Published version | ||||||
| Copyright: | Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0 | ||||||
| Full Text Status: | Public | ||||||
| Subjects: | (A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Biochemistry and Molecular Biology | ||||||
| Keywords: | thymidine kinase 2, mutagenesis, substrate binding, ATP, Mg2+ binding, enzyme kinetics | ||||||
| URN:NBN: | urn:nbn:se:slu:epsilon-p-116661 | ||||||
| Permanent URL: | http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-116661 | ||||||
| Additional ID: |
| ||||||
| ID Code: | 27537 | ||||||
| Faculty: | VH - Faculty of Veterinary Medicine and Animal Science | ||||||
| Department: | (VH) > Dept. of Anatomy, Physiology and Biochemistry | ||||||
| Deposited By: | SLUpub Connector | ||||||
| Deposited On: | 12 Apr 2022 15:37 | ||||||
| Metadata Last Modified: | 12 Apr 2022 15:41 |
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