Investigation of the PDZ domain ligand binding site using chemically modified peptides.
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.
Novak
Kathleen A P
KA
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143-0446, USA.
Fujii
Naoaki
N
Guy
R Kiplin
RK
D000595:Amino Acid Sequence; D001665:Binding Sites; D051528:Guanylate Kinases; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry* / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D008024:Ligands; D009842:Oligopeptides; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases