7P0F

Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic inhibitor HTL0028125

7P0F の概要

• エントリーDOI: 10.2210/pdb7p0f/pdb
• 関連するPDBエントリー: 6ZIS
• 関連するBIRD辞書のPRD_ID: PRD_900001
• 分子名称: 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)
• 機能のキーワード: gpcr, cgrp, ectodomain, inhibitor, macrocycle, membrane protein
• 由来する生物種: Escherichia coli (strain K12); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 67561.83

構造登録者

Southall, S.M.,Watson, S.P. (登録日: 2021-06-29, 公開日: 2022-06-15, 最終更新日: 2024-01-31)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.85 Å)