title: Selectivity mechanism of a bacterial homolog of the human drug-peptide transporters PepT1 and PepT2.
abstract: 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.
authors: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors: Fatma
authors: F
authors: Guettou
authors: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors: Esben M
authors: EM
authors: Quistgaard
authors: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors: Michael
authors: M
authors: Raba
authors: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors: Per
authors: P
authors: Moberg
authors: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors: Christian
authors: C
authors: Löw
authors: 1] Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. [2] School of Biological Sciences, Nanyang Technological University, Singapore. [3] Institute of Molecular and Cell Biology, A* STAR, Singapore.
authors: Pär
authors: P
authors: Nordlund
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008958:Models, Molecular; D000074011:Peptide Transporter 1; D020592:Shewanella / Q000201:enzymology*; D040681:Structural Homology, Protein; D013379:Substrate Specificity; D027981:Symporters / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D000074011:Peptide Transporter 1; D027981:Symporters; C093694:hydrogen-coupled oligopeptide transporter PepT2