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Thymidine kinase 1 regulatory fine-tuning through tetramer formation.

Mutahir, Zeeshan LU ; Clausen, Anders Ranegaard LU ; Andersson, Karl-Magnus LU ; Mebrahtu Wisén, Sofia LU ; Munch-Petersen, Birgitte LU and Piskur, Jure LU (2013) In The FEBS Journal 280(6). p.1531-1541
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Thymidine kinase 1, Regulatory switch, Evolution of enzyme regulation, Oligomerization
in
The FEBS Journal
volume
280
issue
6
pages
1531 - 1541
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000316258400012
  • pmid:23351158
  • scopus:84875301630
  • pmid:23351158
ISSN
1742-464X
DOI
10.1111/febs.12154
language
English
LU publication?
yes
id
06ca2cfb-2e4a-420e-a9a1-d5ae92177538 (old id 3438278)
date added to LUP
2016-04-01 10:30:39
date last changed
2019-03-27 01:16:05
@article{06ca2cfb-2e4a-420e-a9a1-d5ae92177538,
  abstract     = {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.},
  author       = {Mutahir, Zeeshan and Clausen, Anders Ranegaard and Andersson, Karl-Magnus and Mebrahtu Wisén, Sofia and Munch-Petersen, Birgitte and Piskur, Jure},
  issn         = {1742-464X},
  language     = {eng},
  number       = {6},
  pages        = {1531--1541},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {The FEBS Journal},
  title        = {Thymidine kinase 1 regulatory fine-tuning through tetramer formation.},
  url          = {http://dx.doi.org/10.1111/febs.12154},
  doi          = {10.1111/febs.12154},
  volume       = {280},
  year         = {2013},
}