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=== 1. Binding Pocket ===
=== 1. Binding Pocket ===


MRGPRX2 consists of two binding pockets (seen in Figure 2). Sub-pocket 1 consists of primarily hydrophobic aromatic residues; Phe-170, Trp-243, and Phe-244.<ref name="Yang">Yang, Fan, et al. "Structure, function and pharmacology of human itch receptor complexes." Nature, Nature Publishing Group, 17 November 2021, https://www.nature.com/articles/s41586-021-04077-y</ref> These residues provide stabilization with ligands through stacking. This pocket also contains acidic catalytic residues Asp-184 and Glu-164 that interact with substrates by making ion pairs. Lastly, this pocket is in close proximity with the commonly conserved disulfide bond (formed by Cys-168 and Cys-180) seen in most Class A GPCRs. The second binding pocket forms electrostatic interactions with larger substrates (seen in Figure 2), but is generally less studied.<ref name="Cao"/>
MRGPRX2 consists of two binding pockets (seen in Figure 2). Sub-pocket 1 consists of acidic catalytic residues Asp-184 and Glu-164 that interact with substrates by making ion pairs. There are also some hydrophobic aromatic residues, Phe-170, Trp-243, and Phe-244, towards the top of the binding pocket.<ref name="Yang">Yang, Fan, et al. "Structure, function and pharmacology of human itch receptor complexes." Nature, Nature Publishing Group, 17 November 2021, https://www.nature.com/articles/s41586-021-04077-y</ref> These residues provide stabilization with ligands through stacking. Lastly, this pocket is in close proximity with the commonly conserved disulfide bond (formed by Cys-168 and Cys-180) seen in most Class A GPCRs. The second binding pocket forms hydrophobic interactions with larger substrates (seen in Figure 2), but is generally less studied.<ref name="Cao"/>


[[Image:Electro.PNG|450px|center|thumb|'''Figure 2''': Binding pocket of MRGPRX2 with cortistatin-14. Two different binding pockets are present in MRGPRX2 and cortistatin-14 interacts with both of them. <ref name="Cao"/>]]  
[[Image:Electro.PNG|450px|center|thumb|'''Figure 2''': Binding pocket of MRGPRX2 with cortistatin-14. Two different binding pockets are present in MRGPRX2 and cortistatin-14 interacts with both of them. <ref name="Cao"/>]]