8D52

Parathyroid hormone 1 receptor extracellular domain complexed with a peptide ligand containing (2-naphthyl)-beta-3-homoalanine

8D52 の概要

• エントリーDOI: 10.2210/pdb8d52/pdb
• 分子名称: Parathyroid hormone/parathyroid hormone-related peptide receptor, PTHrP[1-36], 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: parathyroid hormone 1 receptor, signaling, beta-amino acid, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 14956.44

構造登録者

Yu, Z.,Kreitler, D.F.,Gellman, S.H. (登録日: 2022-06-03, 公開日: 2023-06-14, 最終更新日: 2024-11-13)

主引用文献

Yu, Z.,Kreitler, D.F.,Chiu, Y.T.T.,Xu, R.,Bruchs, A.T.,Bingman, C.A.,Gellman, S.H.
Harnessing Aromatic-Histidine Interactions through Synergistic Backbone Extension and Side Chain Modification.
Angew.Chem.Int.Ed.Engl., 62:e202308100-e202308100, 2023

PubMed Abstract: Peptide engineering efforts have delivered drugs for diverse human diseases. Side chain alteration is among the most common approaches to designing new peptides for specific applications. The peptide backbone can be modified as well, but this strategy has received relatively little attention. Here we show that new and favorable contacts between a His side chain on a target protein and an aromatic side chain on a synthetic peptide ligand can be engineered by rational and coordinated side chain modification and backbone extension. Side chain modification alone was unsuccessful. Binding measurements, high-resolution structural studies and pharmacological outcomes all support the synergy between backbone and side chain modification in engineered ligands of the parathyroid hormone receptor-1, which is targeted by osteoporosis drugs. These results should motivate other structure-based designs featuring coordinated side chain modification and backbone extension to enhance the engagement of peptide ligands with target proteins.

PubMed: 37587780
DOI: 10.1002/anie.202308100

実験手法

X-RAY DIFFRACTION (2.02 Å)