Sandbox Reserved 1646: Difference between revisions
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The overall pocket in GnRH1R is defined by the N terminus, TM2, TM3, TM5, TM6, and TM7, forming a highly hydrophobic <scene name='86/868179/Gnrh1_colored/5'>binding site</scene> with a few polar residues (D98, N102, K121, and N305) | The overall pocket in GnRH1R is defined by the N terminus, TM2, TM3, TM5, TM6, and TM7, forming a highly hydrophobic <scene name='86/868179/Gnrh1_colored/5'>binding site</scene> with a few polar residues (D98, N102, K121, and N305) | ||
The orthosteric binding pocket of GnRH1R is solvent-accessible, appears relatively shallow and a plasticity is indicated with respect to different ligands. Structural analysis provides the possibility to design orally deliverable small molecules with activity towards the receptor. | The orthosteric binding pocket of GnRH1R is solvent-accessible, appears relatively shallow and a plasticity is indicated with respect to different ligands. Structural analysis provides the possibility to design orally deliverable small molecules with activity towards the receptor. | ||
A detailed interaction network for elagolix has been described | A detailed interaction network for elagolix has been described<ref>DOI: 10.1038/s41467-020-19109-w</ref> in which The N-terminus, residue Y2836.51 and a polar interaction network formed by residues D98 and K121 are of particular importance for ligand recognition. | ||
'''N terminus:''' fits in cavity (contact to surrounding ressiudues: N1022.65, Q1744.60, and F1784.64 from TM2 and TM4) indicating a distinct roles in mediating binding of different ligands. However, it is not engaged in GnRH activation of wild-type GnRH1R. | '''N terminus:''' fits in cavity (contact to surrounding ressiudues: N1022.65, Q1744.60, and F1784.64 from TM2 and TM4) indicating a distinct roles in mediating binding of different ligands. However, it is not engaged in GnRH activation of wild-type GnRH1R. | ||
