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Sammanfattning

Thymidylate kinase (TMPK) phosphorylates deoxythymidine monophosphate (dTMP) and plays an important role in genome stability. Deficiency in TMPK activity due to genetic alterations of DTYMK, i.e., the gene coding for TMPK, causes severe microcephaly in humans. However, no defects were observed in other tissues, suggesting the existence of a compensatory enzyme for dTTP synthesis. In search for this compensatory enzyme we analyzed 6 isoforms of TMPK mRNA deposited in the GenBank. Of these, only isoform 1 has been characterized and represents the known human TMPK. Our results reveal that isoform 2, 3, 4 and 5 lack essential structural elements for substrate binding and, thus, they are considered as nonfunctional isoforms. Isoform 6, however, has intact catalytic centers, i.e., dTMP-binding, DRX motif, ATP-binding p-loop and lid region, which are the key structural elements of an active TMPK, suggesting that isoform 6 may function as TMPK. When isoform 6 was expressed and purified, it showed only minimal activity (

Nyckelord

Thymidylate kinase; TMPK; Isoforms; DTYMK; human

Publicerad i

Nucleosides, Nucleotides and Nucleic Acids
2022, volym: 41, nummer: 3, sidor: 321-332

SLU författare

Globala målen (SDG)

SDG3 God hälsa och välbefinnande

UKÄ forskningsämne

Biokemi
Molekylärbiologi
Medicinsk genetik och genomik

Publikationens identifierare

  • DOI: https://doi.org/10.1080/15257770.2021.2023748

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/115184