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Esben Meldgaard Høgh Quistgaard

Selectivity mechanism of a bacterial homolog of the human drug-peptide transporters PepT1 and PepT2

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DOI

  • Fatma Guettou, Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
  • ,
  • Esben M Quistgaard
  • Michael Raba, Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
  • ,
  • Per Moberg, Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
  • ,
  • Christian Löw, Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden.
  • ,
  • Pär Nordlund, 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.

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.

Original languageEnglish
JournalNature Structural and Molecular Biology
Volume21
Issue8
Pages (from-to)728-31
Number of pages4
ISSN1545-9993
DOIs
Publication statusPublished - Aug 2014
Externally publishedYes

    Research areas

  • Bacterial Proteins, Binding Sites, Crystallography, X-Ray, Humans, Hydrophobic and Hydrophilic Interactions, Kinetics, Models, Molecular, Shewanella, Structural Homology, Protein, Substrate Specificity, Symporters, Journal Article, Research Support, Non-U.S. Gov't

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