8AX7
Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic inhibitor HTL0031448
Summary for 8AX7
| Entry DOI | 10.2210/pdb8ax7/pdb |
| Related PRD ID | PRD_900001 |
| Descriptor | Maltose/maltodextrin-binding periplasmic protein,Receptor activity-modifying protein 1,Calcitonin gene-related peptide type 1 receptor, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, TETRAETHYLENE GLYCOL, ... (6 entities in total) |
| Functional Keywords | cgrp, cgrpr, ectodomain, ramp, macrocycle, macrocyclic, membrane protein |
| Biological source | Escherichia coli K-12 More |
| Total number of polymer chains | 1 |
| Total formula weight | 67636.87 |
| Authors | Southall, S.M.,Watson, S.P. (deposition date: 2022-08-30, release date: 2022-12-07, Last modification date: 2024-10-23) |
| Primary citation | Southall, S.M.,Banerjee, J.,Brown, J.,Butkovic, K.,Cansfield, A.D.,Cansfield, J.E.,Congreve, M.S.,Cseke, G.,Deflorian, F.,Hunjadi, M.P.,Hutinec, A.,Inturi, T.K.,Rupcic, R.,Saxty, G.,Watson, S.P. Novel Macrocyclic Antagonists of the CGRP Receptor Part 2: Stereochemical Inversion Induces an Unprecedented Binding Mode. Acs Med.Chem.Lett., 13:1776-1782, 2022 Cited by PubMed Abstract: The diastereomeric macrocyclic calcitonin gene-related peptide (CGRP) antagonists HTL0029881 () and HTL0029882 (), in which the stereochemistry of a spiro center is reversed, surprisingly demonstrate comparable potency. X-ray crystallographic characterization demonstrates that binds to the CGRP receptor in a precedented manner but that binds in an unprecedented, unexpected, and radically different manner. The observation of this phenomenon is noteworthy and may open novel avenues for CGRP receptor antagonist design. PubMed: 36385934DOI: 10.1021/acsmedchemlett.2c00400 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.65 Å) |
Structure validation
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