Exploiting temperature-dependent substrate promiscuity for nucleoside analogue activation by thymidine kinase from Thermotoga maritima Article

Lutz, S, Lichter, J, Liu, L. (2007). Exploiting temperature-dependent substrate promiscuity for nucleoside analogue activation by thymidine kinase from Thermotoga maritima . JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 129(28), 8714-8715. 10.1021/ja0734391

cited authors

  • Lutz, S; Lichter, J; Liu, L

authors

abstract

  • Enzymes from thermophilic and hyperthermophilic organisms are invaluable catalysts for organic synthesis and biotechnology due to their stability and function at elevated temperatures. While the temperature dependency of catalysis with normal substrates has been studied for several of these enzymes, little is known about the effects of temperature on substrate specificity. Here we report the characterization of a novel thymidine kinase from the hyperthermophilic Thermotoga maritima which shows high substrate specificity at the organism's native growth temperature (82 °C) but turns promiscuous at 37 °C. Our experiments link this temperature-dependent substrate promiscuity to conformational changes in the protein below 70 °C, shifting the enzyme's rate-determining step to a substrate-independent transition in the homotetramer structure. Copyright © 2007 American Chemical Society.

publication date

  • July 18, 2007

published in

Digital Object Identifier (DOI)

start page

  • 8714

end page

  • 8715

volume

  • 129

issue

  • 28