Structure-based synthetic mimicry of discontinuous protein binding sites: inhibitors of the interaction of Mena EVH1 domain with proline-rich ligands.

2.50
Hdl Handle:
http://hdl.handle.net/10033/12430
Title:
Structure-based synthetic mimicry of discontinuous protein binding sites: inhibitors of the interaction of Mena EVH1 domain with proline-rich ligands.
Authors:
Hunke, Cornelia; Hirsch, Tatjana; Eichler, Jutta
Abstract:
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.
Citation:
Chembiochem 2006, 7(8):1258-64
Issue Date:
1-Aug-2006
URI:
http://hdl.handle.net/10033/12430
DOI:
10.1002/cbic.200500465
PubMed ID:
16810654
Type:
Article
Language:
en
ISSN:
1439-4227
Appears in Collections:
Publications from Division of Molekulare Struktur Biologie (MOSB)

Full metadata record

DC FieldValue Language
dc.contributor.authorHunke, Cornelia-
dc.contributor.authorHirsch, Tatjana-
dc.contributor.authorEichler, Jutta-
dc.date.accessioned2007-06-25T14:52:40Z-
dc.date.available2007-06-25T14:52:40Z-
dc.date.issued2006-08-01-
dc.identifier.citationChembiochem 2006, 7(8):1258-64en
dc.identifier.issn1439-4227-
dc.identifier.pmid16810654-
dc.identifier.doi10.1002/cbic.200500465-
dc.identifier.urihttp://hdl.handle.net/10033/12430-
dc.description.abstractThe 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.en
dc.format.extent445080 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoenen
dc.titleStructure-based synthetic mimicry of discontinuous protein binding sites: inhibitors of the interaction of Mena EVH1 domain with proline-rich ligands.en
dc.typeArticleen
dc.format.digYES-

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