5J89

Structure of human Programmed cell death 1 ligand 1 (PD-L1) with low molecular mass inhibitor

5J89 の概要

• エントリーDOI: 10.2210/pdb5j89/pdb
• 分子名称: Programmed cell death 1 ligand 1, N-{2-[({2-methoxy-6-[(2-methyl[1,1'-biphenyl]-3-yl)methoxy]pyridin-3-yl}methyl)amino]ethyl}acetamide, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: pd-l1, programmed cell death 1 ligand 1, cell cycle, immune system
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Isoform 1: Cell membrane ; Single-pass type I membrane protein . Isoform 2: Endomembrane system ; Single-pass type I membrane protein : Q9NZQ7
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 67838.12

構造登録者

Zak, K.M.,Grudnik, P.,Guzik, K.,Zieba, B.J.,Musielak, B.,Doemling, P.,Dubin, G.,Holak, T.A. (登録日: 2016-04-07, 公開日: 2016-04-27, 最終更新日: 2024-11-13)

主引用文献

Zak, K.M.,Grudnik, P.,Guzik, K.,Zieba, B.J.,Musielak, B.,Domling, A.,Dubin, G.,Holak, T.A.
Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1).
Oncotarget, 7:30323-30335, 2016

PubMed Abstract: Targeting the PD-1/PD-L1 immunologic checkpoint with monoclonal antibodies has provided unprecedented results in cancer treatment in the recent years. Development of chemical inhibitors for this pathway lags the antibody development because of insufficient structural information. The first nonpeptidic chemical inhibitors that target the PD-1/PD-L1 interaction have only been recently disclosed by Bristol-Myers Squibb. Here, we show that these small-molecule compounds bind directly to PD-L1 and that they potently block PD-1 binding. Structural studies reveal a dimeric protein complex with a single small molecule which stabilizes the dimer thus occluding the PD-1 interaction surface of PD-L1s. The small-molecule interaction "hot spots" on PD-L1 surfaces suggest approaches for the PD-1/PD-L1 antagonist drug discovery.

PubMed: 27083005
DOI: 10.18632/oncotarget.8730

実験手法

X-RAY DIFFRACTION (2.2 Å)