Investigation of the PDZ domain ligand binding site using chemically modified peptides

Bioorg Med Chem Lett. 2002 Sep 2;12(17):2471-4. doi: 10.1016/s0960-894x(02)00345-1.


Several chemically modified analogues to a tightly binding ligand for the second PDZ domain of MAGI-3 were synthesized and evaluated for their ability to compete with native peptide ligands. N-methyl scanning of the ligand backbone amides revealed the energetically important hydrogen bonds between the ligand backbone and the PDZ domain. Analogues to the ligand's conserved threonine/serine(-2) residue, involved in a side chain to side chain hydrogen bond with a conserved histidine in the PDZ domain, revealed that the interaction is highly sensitive to the steric structure around the hydroxyl group of this residue. Analogues of the ligand carboxy terminus revealed that the full hydrogen bond network of the GLGF loop is important in ligand binding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Guanylate Kinases
  • Humans
  • Hydrogen Bonding
  • Ligands
  • Nucleoside-Phosphate Kinase / chemistry*
  • Nucleoside-Phosphate Kinase / metabolism
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Structure-Activity Relationship


  • Ligands
  • Oligopeptides
  • Nucleoside-Phosphate Kinase
  • Guanylate Kinases