Fig. 3

Substrate-binding pocket of YePEPT. Top view from the cytosol (a) and view from the membrane plane (d) of the substrate-binding pocket of YePEPT. The areas marked by the black boxes in (a) and (d) are displayed at higher magnification in (b) and (c), and (e) and (f), respectively. Amino acid residues of YePEPT potentially involved in alafosfalin (in yellow; (b) and (e)) and dipeptide backbone binding (Ala-Phe dipeptide in green; panels (c) and (f)) are labeled, colored in black and conserved in YePEPT, GkPOT^E310Q and PepT_St (see Additional file 6: Table S2 for more details and groups of conserved amino acid residues involved in alafosfalin and Ala-Phe dipeptide backbone binding). The indicated amino acid residues of YePEPT were identified by superposition of the YePEPT structure with the ligand-bound peptide transporter structures 4D2C [8] and 4IKZ [9] (PDB ID codes). The distances between the nitrogen atom of Lys314 and the carbon atoms of the N-terminally located methyl groups of alafosfalin (e) and Ala-Phe (f) are marked, and indicate available space between ligands and Lys314; for example, for accommodation of longer side chains. The N- and C-terminal six-helix bundles are colored in salmon and cyan, respectively, and helices HA and HB in black. YePEPT polypeptide chains in (a) and (d) that could not be traced are indicated by broken lines