7P0I

Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic inhibitor Compound 13

Summary for 7P0I

• Entry DOI: 10.2210/pdb7p0i/pdb
• Related: 7P0F
• 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, ... (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: 67698.96

Authors

Southall, S.M. (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

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: 35245037
DOI: 10.1021/acschemneuro.1c00696

Experimental method

X-RAY DIFFRACTION (2.3 Å)