Thermodynamic analysis of a hydrophobic binding site: probing the PDZ domain with nonproteinogenic peptide ligands.

Journal Article (Journal Article)

[structure: see text] Isothermal titration calorimetry (ITC) is used to study the thermodynamic consequences of systematically modifying the hydrophobic character of a single residue in a series of protein-binding ligands. By substituting standard and nonproteinogenic aliphatic amino acids for the C-terminal valine of the hexapeptide KKETEV, binding to the third PDZ domain (PDZ3) of the PSD-95 protein is characterized by distinct changes in the Gibbs free energy (DeltaG), enthalpy (DeltaH), and entropy (TDeltaS) parameters. One notable observation is that peptide binding affinity can be improved with a nonstandard residue.

Full Text

Duke Authors

Cited Authors

  • Saro, D; Klosi, E; Paredes, A; Spaller, MR

Published Date

  • September 2004

Published In

Volume / Issue

  • 6 / 20

Start / End Page

  • 3429 - 3432

PubMed ID

  • 15387515

Electronic International Standard Serial Number (EISSN)

  • 1523-7052

International Standard Serial Number (ISSN)

  • 1523-7060

Digital Object Identifier (DOI)

  • 10.1021/ol049181q

Language

  • eng