Selectivity mechanism of a bacterial homolog of the human drug-peptide transporters PepT1 and PepT2
| Autor: | Fatma Guettou, Pär Nordlund, Esben M. Quistgaard, Michael Raba, Per Moberg, Christian Löw |
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| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Shewanella Stereochemistry Peptide Tripeptide Crystallography X-Ray Peptide Transporter 1 Substrate Specificity Bacterial Proteins Structural Biology Side chain Humans Shewanella oneidensis Binding site Molecular Biology chemistry.chemical_classification Binding Sites Symporters biology Chemistry Peptide transporter 1 Transporter biology.organism_classification Kinetics Biochemistry Membrane protein Structural Homology Protein biology.protein Hydrophobic and Hydrophilic Interactions |
| Zdroj: | Nature Structural & Molecular Biology. 21:728-731 |
| ISSN: | 1545-9985 1545-9993 |
| DOI: | 10.1038/nsmb.2860 |
| Popis: | Peptide transporters of the PepT family have key roles in the transport of di- and tripeptides across membranes as well as in the absorption of orally administered drugs in the small intestine. We have determined structures of a PepT transporter from Shewanella oneidensis (PepT(So2)) in complex with three different peptides. The peptides bind in a large cavity lined by residues that are highly conserved in human PepT1 and PepT2. The bound peptides adopt extended conformations with their N termini clamped into a conserved polar pocket. A positively charged patch allows differential interactions with the C-terminal carboxylates of di- and tripeptides. Here we identify three pockets for peptide side chain interactions, and our binding studies define differential roles of these pockets for the recognition of different subtypes of peptide side chains. |
| Databáze: | OpenAIRE |
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