English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse
  1. View item / 
  2. Item Summary

Item

ITEM ACTIONSEXPORT
Add to Basket
  Local TagsRelease HistoryDetailsSummary

Released
Journal Article

Modifying human thymidylate kinase to potentiate azidothymidine activation

MPS-Authors
/persons/resource/persons94928

Reinstein,  Jochen
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons95189

Schlichting,  Ilme
Emeritus Group Biophysics, Max Planck Institute for Medical Research, Max Planck Society;

/persons/resource/persons93142

Goody,  Roger S.
Emeritus Group Biophysics, Max Planck Institute for Medical Research, Max Planck Society;

External Resource

http://www.jbc.org/content/274/50/35289.full.pdf
(Any fulltext)

https://dx.doi.org/10.1074/jbc.274.50.35289
(Any fulltext)

Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Brundiers, R., Lavie, A., Veit, T., Reinstein, J., Schlichting, I., Ostermann, N., et al. (1999). Modifying human thymidylate kinase to potentiate azidothymidine activation. The Journal of Biological Chemistry, 274(50), 35289-35292. doi:10.1074/jbc.274.50.35289.


Cite as: https://hdl.handle.net/11858/00-001M-0000-002C-2262-5
Abstract
Based on the knowledge of the crystal structures of yeast and Escherichia coli thymidylate kinases (TmpKs) and the observation that TmpK from E. coli can phosphorylate azidothymidine monophosphate (AZT-MP) much more efficiently than either the yeast or the highly homologous human enzyme, we have engineered yeast and human TmpKs to obtain enzymes that have dramatically improved AZT-MP phosphorylation properties. These modified enzymes have properties that make them attractive candidates for gene therapeutic approaches to potentiating the action of AZT as an inhibitor of human immunodeficiency virus (HIV) replication. In particular, insertion of the lid domain of the bacterial TmpK into the human enzyme results in a pronounced change of the acceptance of AZT-MP such that it is now phosphorylated even faster than TMP.