FIGURE 7.

Co-structural model of syntenin-1 PDZ2-binding syndecan-1 peptide QEEFpYA. Two models of the syntenin-1 PDZ2-binding syndecan-1 QEEFpYA (A) or QEEFYA (B) structures were generated using the x-ray-derived coordinate of the syntenin-1 PDZ2-binding syndecan-4 peptide TNEFYA (Protein Data Bank accession number 1OBY) (29) as a template. The Tyr-1 is in a groove formed by Thr-206, Phe-211, and Ile-212, which orient its aromatic cycle. This groove is well adapted to the size of the Tyr cycle but is too narrow when the latter contains a phosphate on its hydroxyl function. Furthermore, the contact of the phosphate group with the PDZ2 Asp-204 is unfavorable in term of columbic energy of interaction. Finally, the Tyr-1 hydrogen bond with Thr-206 and the π-stacking of its aromatic ring with His-208 are lost when the Tyr-1 is phosphorylated. The binding energy of the peptide to the PDZ2 was computed using the ZAP algorithm, which is an enhancement of the Poisson-Boltzmann equation, allowing computing of the binding energy of two biopolymers. This energy was computed for the two peptides complexes with the syntenin-1. The binding energies are about -2.92 kcal·mol^-1 for the phosphorylated Tyr-1 and -18.31 kcal·mol^-1 for the unphosphorylated Tyr-1. The color of the surface is mapped with atomic partial charge. Negative charge is colored in blue, neutral charge is in white, and positive charge is in red.