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Table 4 CCK-2R mutagenesis data and their correspondence to our model (ref. [27] and references therein)

From: Structural studies on radiopharmaceutical DOTA-minigastrin analogue (CP04) complexes and their interaction with CCK2 receptor

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