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Structure‐Based Synthetic Mimicry of Discontinuous Protein Binding Sites: Inhibitors of the Interaction of Mena EVH1 Domain with Proline‐Rich Ligands
Author(s) -
Hunke Cornelia,
Hirsch Tatjana,
Eichler Jutta
Publication year - 2006
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200500465
Subject(s) - polyproline helix , ligand (biochemistry) , binding domain , plasma protein binding , binding site , proline , peptide , biology , biochemistry , chemistry , biophysics , microbiology and biotechnology , amino acid , receptor
The Mena EVH1 domain, a protein‐interaction module involved in actin‐based cell motility, recognizes proline‐rich ligand motifs, which are also present in the sequence of the surface protein ActA of Listeria monocytogenes . The interaction of ActA with host Mena EVH1 enables the bacterium to actively recruit host actin in order to spread into neighboring cells. Based on the crystal structure of Mena EVH1 in complex with a polyproline peptide ligand, we have generated a range of assembled peptides presenting the Mena EVH1 fragments that make up its discontinuous binding site for proline‐rich ligands. Some of these peptides were found to inhibit the interaction of Mena EVH1 with the ligand pGolemi. One of them was further characterized at the level of individual amino acid residues; this yielded information on the contribution of individual positions of the peptides to the interaction with the ligand and identified sites for future structure optimization.