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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