7OUN

Structure of human PD-L1 in complex with macrocyclic inhibitor

7OUN の概要

• エントリーDOI: 10.2210/pdb7oun/pdb
• 分子名称: Programmed cell death 1 ligand 1, macrocyclic peptide (3 entities in total)
• 機能のキーワード: programmed death ligand 1, immune checkpoint inhibitor, cancer, cell cycle, immune system
• 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: 16494.92

構造登録者

Zyla, E.,Dubin, G. (登録日: 2021-06-12, 公開日: 2021-09-15, 最終更新日: 2024-10-23)

主引用文献

Zyla, E.,Musielak, B.,Holak, T.A.,Dubin, G.
Structural Characterization of a Macrocyclic Peptide Modulator of the PD-1/PD-L1 Immune Checkpoint Axis.
Molecules, 26:-, 2021

PubMed Abstract: The clinical success of PD-1/PD-L1 immune checkpoint targeting antibodies in cancer is followed by efforts to develop small molecule inhibitors with better penetration into solid tumors and more favorable pharmacokinetics. Here we report the crystal structure of a macrocyclic peptide inhibitor (peptide 104) in complex with PD-L1. Our structure shows no indication of an unusual bifurcated binding mode demonstrated earlier for another peptide of the same family (peptide 101). The binding mode relies on extensive hydrophobic interactions at the center of the binding surface and an electrostatic patch at the side. An interesting sulfur/π interaction supports the macrocycle-receptor binding. Overall, our results allow a better understanding of forces guiding macrocycle affinity for PD-L1, providing a rationale for future structure-based inhibitor design and rational optimization.

PubMed: 34443436
DOI: 10.3390/molecules26164848

実験手法

X-RAY DIFFRACTION (1.9 Å)