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Transferred Cross-Correlated Relaxation: Application to Drug/Target Complexes

  • T. Carlomagno
  • C.  Griesinger

The NMR spectra of biomolecules without and especially with isotopic labeling provide a wealth of information about interatomic distances and angular geometries that can be used as conformational restraints in structure determination. In this review we will focus on the application of cross-correlated relaxation rates to obtain structural information on a small-molecule/protein complex that has pharmaceutical implications. Cross-correlated relaxation complements information derived from NOEs. The chosen complex: epothilone/tubulin could not be subjected to X-ray crystallography. Electron microscopy can only be performed on tubulin sheets induced with Zn ions, which show an assembly of the tubulin dimers that is not found under physiological conditions. A structure of epothilone when bound to tubulin has been determined by electron crystallography. However, the resolution is too low to deduce the conformation of epothilone in a unique way. Thus, NMR constitutes a unique tool for the investigation of this drug/protein complex to obtain a highresolution structure of the drug molecule in the bound state.

Keywords

Cross Peak Reference Experiment Tensorial Interaction Electron Crystallography Angular Geometry 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer 2008

Authors and Affiliations

  • T. Carlomagno
    • 1
  • C.  Griesinger
    • 1
  1. 1.Max Planck Institut for Biophysical ChemistryGöttingenGermany

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