6YEA

Human wtSTING in complex with 2',2'-difluoro-3',3'-cGAMP

6YEA の概要

• エントリーDOI: 10.2210/pdb6yea/pdb
• 分子名称: Stimulator of interferon protein, 2',2'-difluoro-3',3'-cGAMP (3 entities in total)
• 機能のキーワード: innate immune system, cyclic dinucleotide, sting, protein binding
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23867.46

構造登録者

Boura, E.,Smola, M. (登録日: 2020-03-24, 公開日: 2021-03-31, 最終更新日: 2024-01-24)

主引用文献

Smola, M.,Gutten, O.,Dejmek, M.,Kozisek, M.,Evangelidis, T.,Tehrani, Z.A.,Novotna, B.,Nencka, R.,Birkus, G.,Rulisek, L.,Boura, E.
Ligand Strain and Its Conformational Complexity Is a Major Factor in the Binding of Cyclic Dinucleotides to STING Protein.
Angew.Chem.Int.Ed.Engl., 60:10172-10178, 2021

PubMed Abstract: STING (stimulator of interferon genes) is a key regulator of innate immunity that has recently been recognized as a promising drug target. STING is activated by cyclic dinucleotides (CDNs) which eventually leads to expression of type I interferons and other cytokines. Factors underlying the affinity of various CDN analogues are poorly understood. Herein, we correlate structural biology, isothermal calorimetry (ITC) and computational modeling to elucidate factors contributing to binding of six CDNs-three pairs of natural (ribo) and fluorinated (2'-fluororibo) 3',3'-CDNs. X-ray structural analyses of six {STING:CDN} complexes did not offer any explanation for the different affinities of the studied ligands. ITC showed entropy/enthalpy compensation up to 25 kcal mol for this set of similar ligands. The higher affinities of fluorinated analogues are explained with help of computational methods by smaller loss of entropy upon binding and by smaller strain (free) energy.

PubMed: 33616279
DOI: 10.1002/anie.202016805

実験手法

X-RAY DIFFRACTION (2.805 Å)