Sandbox Reserved 1719: Difference between revisions
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== Ligand interactions == | == Ligand interactions == | ||
*<scene name='90/904324/C4880/8'>C48/80</scene> | *<scene name='90/904324/C4880/8'>C48/80</scene> | ||
**C48/80 is a peptide limetic agonist that can bind to MRGPRX2 when it is associated with a G<sub>i</sub> or G<sub>q</sub> protein.<ref name= "Yang">DOI: 10.1038/s41586-021-04077-y</ref> The structure of the ligand consists of three phenethylamine groups that are arranged in a Y shape with a semicircular arrangement ('''Figure 4''').<ref name="Yang"/> Upon its binding, the Asp184 and Glu164 residues within sub-pocket 1 interact only with the central phenethylamine ring, forming hydrogen bonds and charge-charge interactions.<ref name="Yang"/> | **C48/80 is a peptide limetic agonist that can bind to MRGPRX2 when it is associated with a G<sub>i</sub> or G<sub>q</sub> protein.<ref name= "Yang">DOI: 10.1038/s41586-021-04077-y</ref> The structure of the ligand consists of three phenethylamine groups that are arranged in a Y shape with a semicircular arrangement ('''Figure 4''').<ref name="Yang"/> Upon its binding, the Asp184 and Glu164 residues within sub-pocket 1 interact only with the central phenethylamine ring, forming hydrogen bonds and charge-charge interactions.<ref name="Yang"/> | ||
*<scene name='90/904324/Rzinc3573/7'>(R)-zinc-3573</scene> | *<scene name='90/904324/Rzinc3573/7'>(R)-zinc-3573</scene> | ||
**(R)-zinc-3573 is | **(R)-zinc-3573 is a synthetic agonist that binds to MRGPRX2 when it is associated with a G<sub>i</sub> or G<sub>q</sub> protein.<ref name="Can">DOI: 10.1038/s41586-021-04126-6</ref> This agonist is a small cationic molecule that forms largely ionic interactions with the negatively-charged sub-pocket 1 and has no interactions with sub-pocket 2 ('''Figure 4''').<ref name="Can"/> (R)-zinc-3573 forms hydrogen bonds and hydrophobic interactions with Asp184 and Glu164 of sub-pocket 1.<ref name="Can"/><ref>DOI: 10.1038/nchembio.2334</ref> | ||
*<scene name='90/904324/Cortistatin-14/6'>Cortistatin-14</scene> | *<scene name='90/904324/Cortistatin-14/6'>Cortistatin-14</scene> | ||
**Cortistatin-14 is an endogenous, cyclic, neuropeptide agonist which interacts with MRGPRX2 in the same way whether it is coupled to G<sub>i</sub> or G<sub>q</sub> proteins ('''Figure 4''').<ref name="Can"/><ref name= "Jiang">DOI: 10.3389/fphar.2018.00767</ref> Cortistation-14 is widely available in many systems throughout the body and naturally functions to regulate many physiological and pathological mechanisms. The lysine residue (Lys3) on Cortistatin-14 binds in the negatively-charged sub-pocket 1 and forms strong charge interactions with Asp184 and Glu164.<ref name="Can"/> The remaining residues of Cortistatin-14 will extend over to sub-pocket 2 and bind through hydrophobic interactions.<ref name="Can"/> | **Cortistatin-14 is an endogenous, cyclic, neuropeptide agonist which interacts with MRGPRX2 in the same way whether it is coupled to G<sub>i</sub> or G<sub>q</sub> proteins ('''Figure 4''').<ref name="Can"/><ref name= "Jiang">DOI: 10.3389/fphar.2018.00767</ref> Cortistation-14 is widely available in many systems throughout the body and naturally functions to regulate many physiological and pathological mechanisms. The lysine residue (Lys3) on Cortistatin-14 binds in the negatively-charged sub-pocket 1 and forms strong charge interactions with Asp184 and Glu164.<ref name="Can"/> The remaining residues of Cortistatin-14 will extend over to sub-pocket 2 and bind through hydrophobic interactions.<ref name="Can"/> | ||
[[Image:Ligands3.png|600px|center|thumb|'''Figure 4.''' Common MRGPRX2 ligand structures and interactions. Hydrophobic interactions are shown by dashed wheat lines indicating direction. Positive atoms are represented in blue. Negative atoms are represented in red.]] | |||
== Differences to most class A GPCRs == | == Differences to most class A GPCRs == | ||
