Temperature dependence of ligand-protein complex formation as reflected by saturation transfer difference NMR experiments

Patrick Groves, Katalin E. Kövér, Sabine André, Joanna Bandorowicz-Pikula, Gyula Batta, Marta Bruix, René Buchet, Angeles Canales, F. Javier Cañada, Hans Joachim Gabius, Douglas V. Laurents, Jose R. Naranjo, Matgorzata Palczewska, Slawomir Pikula, Eduardo Rial, Agnieszka Strzelecka-Kiliszek, Jesús Jiménez-Barbero

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24 Citations (Scopus)

Abstract

We show that temperature is an important parameter for the sensitivity of saturation transfer difference (STD) spectroscopy. A decreased intensity of STD signals is observed for lactose binding to growth-regulatory galectin7 (p53-induced gene 1), as well as for nucleotide binding to annexin A6, when the temperature is increased from 281 to 298-310 K. Opposite temperature effects on STD intensity are observed for S-peptide binding to S-protein to reconstitute RNase S. However, the STD signals for tryptophan binding to downstream regulatory element antagonist modulator of the human prodynorphin gene (DREAM)are relatively unaffected between 281 and 298 K. The known kinetics of the binding of ATP by the uncoupling protein from brown adipose tissue mitochondria (UCPl) predicted an observable STD at 310 K, but rapid sample degradation limits the experiments to much lower temperatures. Temperature strongly influences the kinetics and affinity constant of various types of complex formation and in so doing influences the observed STD effects. Therefore, temperature can be exploited to facilitate the optimization of STD-based applications, and at the same time minimize the number of test samples. STD-based screening protocols to detect new target-specific compounds may yield a larger number of potential ligands if screened at various temperatures.

Original languageEnglish
Pages (from-to)745-748
Number of pages4
JournalMagnetic Resonance in Chemistry
Volume45
Issue number9
DOIs
Publication statusPublished - Sep 2007

Keywords

  • Annexin
  • C
  • Drug discovery
  • Galectin
  • H
  • N
  • NMR
  • RNase S
  • Saturation transfer difference

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)

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    Groves, P., Kövér, K. E., André, S., Bandorowicz-Pikula, J., Batta, G., Bruix, M., Buchet, R., Canales, A., Cañada, F. J., Gabius, H. J., Laurents, D. V., Naranjo, J. R., Palczewska, M., Pikula, S., Rial, E., Strzelecka-Kiliszek, A., & Jiménez-Barbero, J. (2007). Temperature dependence of ligand-protein complex formation as reflected by saturation transfer difference NMR experiments. Magnetic Resonance in Chemistry, 45(9), 745-748. https://doi.org/10.1002/mrc.2041