The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Thymidine kinase 1 regulatory fine-tuning through tetramer formation.

På svenska

Author

  • Zeeshan Mutahir
  • Anders Ranegaard Clausen
  • Karl-Magnus Andersson
  • Sofia Mebrahtu Wisén
  • Birgitte Munch-Petersen
  • Jure Piskur

Summary, in English

Thymidine kinase 1 (TK1) provides a crucial precursor, thymidine monophosphate (dTMP), for nucleic acid synthesis, and the activity of TK1 increases up to 200-fold during the S-phase of cell division in humans. An important part of the regulatory check-points is the ATP and enzyme concentration-dependent transition of TK1 from a dimer with low catalytic efficiency to a tetramer with high catalytic efficiency. This regulatory fine-tuning serves as an additional control to provide the balanced pool of nucleic acid precursors in the cell. We sub-cloned and over-expressed ten different TK1s, originating from widely different organisms, and characterized their kinetic and oligomerization properties. While bacteria, plants and Dictyostelium only exhibited dimeric TK1, we found that all animals had a tetrameric TK1. However, a clear ATP dependent switch between dimer and tetramer was found only in higher vertebrates, and was especially pronounced in mammalian and bird TK1s. We suggest that the dimer form is the original one and the tetramer originated in the animal lineage after the split of Dictyostelium and the lineages leading to invertebrates and vertebrates. The efficient switching mechanism was likely settled first in the warm-blooded animals when they separated from the rest of vertebrates. © 2013 The Authors Journal compilation © 2013 FEBS.

Publishing year

2013

Language

English

Pages

1531-1541

Publication/Series

The FEBS Journal

Volume

280

Issue

6

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Biological Sciences

Keywords

  • Thymidine kinase 1
  • Regulatory switch
  • Evolution of enzyme regulation
  • Oligomerization

Status

Published

ISBN/ISSN/Other

  • ISSN: 1742-464X