7P0F
Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic inhibitor HTL0028125
Summary for 7P0F
| Entry DOI | 10.2210/pdb7p0f/pdb |
| Related | 6ZIS |
| 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, (1S,10R,23E)-12-methyl-10-[(7-methyl-1H-indazol-5-yl)methyl]-15,18,21-trioxa-5,9,12,27,29-pentazapentacyclo[23.5.2.11,4.13,7.028,31]tetratriaconta-3(33),4,6,23,25(32),26,28(31)-heptaene-8,11,30-trione, ... (5 entities in total) |
| Functional Keywords | gpcr, cgrp, ectodomain, inhibitor, macrocycle, membrane protein |
| Biological source | Escherichia coli (strain K12) More |
| Total number of polymer chains | 1 |
| Total formula weight | 67561.83 |
| Authors | Southall, S.M.,Watson, S.P. (deposition date: 2021-06-29, release date: 2022-06-15, Last modification date: 2024-01-31) |
| Primary citation | Cansfield, A.D.,Ator, M.A.,Banerjee, J.,Bestwick, M.,Bortolato, A.,Brown, G.A.,Brown, J.,Butkovic, K.,Cansfield, J.E.,Christopher, J.A.,Congreve, M.,Cseke, G.,Deflorian, F.,Dugan, B.,Hunjadi, M.P.,Hutinec, A.,Inturi, T.K.,Landek, G.,Mason, J.,O'Brien, A.,Ott, G.R.,Rupcic, R.,Saxty, G.,Southall, S.M.,Zadravec, R.,Watson, S.P. Novel Macrocyclic Antagonists of the Calcitonin Gene-Related Peptide Receptor: Design, Realization, and Structural Characterization of Protein-Ligand Complexes. Acs Chem Neurosci, 13:751-765, 2022 Cited by PubMed Abstract: A series of macrocyclic calcitonin gene-related peptide (CGRP) receptor antagonists identified using structure-based design principles, exemplified by HTL0028016 () and HTL0028125 (), is described. Structural characterization by X-ray crystallography of the interaction of two of the macrocycle antagonists with the CGRP receptor ectodomain is described, along with structure-activity relationships associated with point changes to the macrocyclic antagonists. The identification of non-peptidic/natural product-derived, macrocyclic ligands for a G protein coupled receptor (GPCR) is noteworthy. PubMed: 35245037DOI: 10.1021/acschemneuro.1c00696 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.85 Å) |
Structure validation
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