Ligand binding studied by 2D IR spectroscopy using the azidohomoalanine label

J Phys Chem B. 2012 Nov 26;116(46):13705-12. doi: 10.1021/jp3095209. Epub 2012 Nov 9.

Abstract

We explore the capability of the azidohomoalanine (Aha) as a vibrational label for 2D IR spectroscopy to study the binding of the target peptide to the PDZ2 domain. The Aha label responds sensitively to its local environment and its peak extinction coefficient of 350-400 M(-1) cm(-1) is high enough to routinely measure it in the low millimolar concentration regime. The central frequency, inhomogeneous width and spectral diffusion times deduced from the 2D IR line shapes of the Aha label at various positions in the peptide sequence is discussed in relationship to the known X-ray structure of the peptide bound to the PDZ2 domain. The results suggest that the Aha label introduces only a small perturbation to the overall structure of the peptide in the binding pocket. Finally, Aha is a methionine analog that can be incorporated also into larger proteins at essentially any position using protein expression. Altogether, Aha thus fulfills the requirements a versatile label should have for studies of protein structure and dynamics by 2D IR spectroscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / analogs & derivatives*
  • Alanine / chemistry
  • Ligands
  • Models, Molecular
  • Spectrophotometry, Infrared*
  • Staining and Labeling

Substances

  • Ligands
  • azidohomoalanine
  • Alanine