9C3G

human cGAS core domain (K427E/K428E) bound to Cladophorol A

これはPDB形式変換不可エントリーです。

9C3G の概要

• エントリーDOI: 10.2210/pdb9c3g/pdb
• 分子名称: Cyclic GMP-AMP synthase, cladophorol A, ZINC ION, ... (4 entities in total)
• 機能のキーワード: cgas, cgamp, cyclic gmp-amp synthase, dna binding protein, transferase-inhibitor complex, transferase/inhibitor
• 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: 43939.78

構造登録者

Kissai, M.,Stanfield, R.L.,Lairson, L.L. (登録日: 2024-05-31, 公開日: 2025-03-05)

主引用文献

Kissai, M.,Chin, E.N.,Martinez-Pena, F.,Sulpizio, A.,Stout, E.P.,Usui, I.,Barmare, F.,Sanchez, B.,Esquenazi, E.,Stanfield, R.L.,Wilson, I.A.,Lairson, L.L.
Cladophorol-A is an inhibitor of cyclic GMP-AMP synthase.
Bioorg.Med.Chem.Lett., 115:130007-130007, 2025

PubMed Abstract: Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) is an enzyme sensor of double-stranded DNA (dsDNA) that serves to trigger activation of the cGAS-stimulator of interferon genes (STING) pathway. Excessive activation of this pathway has been demonstrated to contribute to various forms of inflammatory disease. As such, cGAS has arisen as a potential therapeutic target with broad potential applications. Using a pathway-targeted cell-based screening approach, we identified the natural product Cladophorol-A as a new class of non-cytotoxic cGAS inhibitor (cell-based IC = 370 nM). An X-ray co-crystal structure at 2.75 Å resolution revealed that Cladophorol-A inhibits cGAS by binding to its active site within the conserved adenosine nucleobase binding site.

PubMed: 39521150
DOI: 10.1016/j.bmcl.2024.130007

実験手法

X-RAY DIFFRACTION (2.75 Å)