Fig. 5: Subtype selectivity between SSTR2 and SSTR4.

a Comparison of the binding mode of octreotide in the docking model and that of SST-14 in the SST-14–SSTR2 complex. Octreotide is shown as teal sticks and SST-14 is shown as orange cartoon and sticks. b Interactions between the key pharmacophore (F7–d-W8–K9–T10) of octreotide and SSTR2. SSTR2 is shown as split-pea cartoon and involved residues are shown as sticks. Polar interactions are indicated by red dash lines. c Comparison of the binding mode of peptide 3 in simulation snapshots of the peptide 3–SSTR4 complex and that of SST-14 in the SST-14–SSTR4 complex. Peptide 3 is shown as raspberry sticks and SST-14 is shown as green cartoon. d Interactions between the key pharmacophore (A7–W8–K9–T10) of peptide 3 and SSTR4. SSTR4 is shown as warm-pink cartoon and involved residues are shown as sticks. e, f Inhibition of forskolin-stimulated cAMP accumulation of WT SSTR2 and SSTR2 mutants induced by octreotide (e) or that of WT SSTR4 and SSTR4 mutants induced by peptide 3 (f). Bars represent the differences between the calculated agonist potency (pEC₅₀) of WT and mutants. The P value was defined as: *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. nd (not determined) indicates that a robust concentration response curve could not be determined within the concentration range tested. ^#Low surface expression level (< 40% of WT expression). Detailed statistical evaluation is shown in Supplementary information, Table S3. g, h Interactions between octreotide and SSTR2 (g) or between peptide 3 and SSTR4 (h). i Sequence alignment of SSTRs. Orange boxes indicate specific residues involved in selective ligand binding.