6VQN

Co-crystal structure of human PD-L1 complexed with Compound A

6VQN の概要

• エントリーDOI: 10.2210/pdb6vqn/pdb
• 分子名称: Programmed cell death 1 ligand 1, N,N'-(2,2'-dimethyl[1,1'-biphenyl]-3,3'-diyl)bis(5-{[(2-hydroxyethyl)amino]methyl}pyridine-2-carboxamide) (3 entities in total)
• 機能のキーワード: complex, cell cycle
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 45567.20

構造登録者

White, A.,Lakshminarasimhan, D.,Leo, C.,Suto, R.K. (登録日: 2020-02-05, 公開日: 2021-01-20, 最終更新日: 2024-10-16)

主引用文献

Park, J.J.,Thi, E.P.,Carpio, V.H.,Bi, Y.,Cole, A.G.,Dorsey, B.D.,Fan, K.,Harasym, T.,Iott, C.L.,Kadhim, S.,Kim, J.H.,Lee, A.C.H.,Nguyen, D.,Paratala, B.S.,Qiu, R.,White, A.,Lakshminarasimhan, D.,Leo, C.,Suto, R.K.,Rijnbrand, R.,Tang, S.,Sofia, M.J.,Moore, C.B.
Checkpoint inhibition through small molecule-induced internalization of programmed death-ligand 1.
Nat Commun, 12:1222-1222, 2021

PubMed Abstract: Programmed death-ligand 1 is a glycoprotein expressed on antigen presenting cells, hepatocytes, and tumors which upon interaction with programmed death-1, results in inhibition of antigen-specific T cell responses. Here, we report a mechanism of inhibiting programmed death-ligand 1 through small molecule-induced dimerization and internalization. This represents a mechanism of checkpoint inhibition, which differentiates from anti-programmed death-ligand 1 antibodies which function through molecular disruption of the programmed death 1 interaction. Testing of programmed death ligand 1 small molecule inhibition in a humanized mouse model of colorectal cancer results in a significant reduction in tumor size and promotes T cell proliferation. In addition, antigen-specific T and B cell responses from patients with chronic hepatitis B infection are significantly elevated upon programmed death ligand 1 small molecule inhibitor treatment. Taken together, these data identify a mechanism of small molecule-induced programmed death ligand 1 internalization with potential therapeutic implications in oncology and chronic viral infections.

PubMed: 33619272
DOI: 10.1038/s41467-021-21410-1

実験手法

X-RAY DIFFRACTION (2.49 Å)