Receptor residue | Mutation | Impact on CCK/gastrin affinity for CCK-2R | Our in silico model |
---|---|---|---|
Thr1112.61 | T111A | Decrease | The residue in the vicinity of Met−3, exchange to Ala gives more void and less tight matching |
Met1343.32 | M134A | Slight increase | Met-3 side chain is predicted to be positioned so that the branched methyl unit of Leu would create a steric clash, however relatively ease to relieve |
M134L | Slight decrease | ||
Tyr1894.61 | Y189A | Drastic drop of CCK affinity | The residue involved in the “aromatic cage,” it interacts with Phe−1 |
His207ECL2 | H207A | Significant decrease in CCK affinity | Earlier reports suggested the interaction between His207ECL2 and Asp−2 of CCK, such a contact is present in our model |
Asn3536.55 | N353L | More hydrophobic Leu improves CCK and gastrin affinity | Participates in hydrophobic contacts with Trp−4 |
N353A | Shorter Ala decreases the affinity | ||
Arg3566.58 | R356D | Large drop in CCK affinity | The residue involved in cation-π interactions, exchange for negatively charged side chain (R->D) should disrupt this interaction, shorter positively charged (R->K/H) or neutral residues (R->A) should bring about some decrease in affinity |
R356A | Decrease less dramatic compared to R356D | ||
R356K/H | Decrease less dramatic compared to R356D |