9C3G
human cGAS core domain (K427E/K428E) bound to Cladophorol A
This is a non-PDB format compatible entry.
Summary for 9C3G
| Entry DOI | 10.2210/pdb9c3g/pdb |
| Descriptor | Cyclic GMP-AMP synthase, cladophorol A, ZINC ION, ... (4 entities in total) |
| Functional Keywords | cgas, cgamp, cyclic gmp-amp synthase, dna binding protein, transferase-inhibitor complex, transferase/inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 43939.78 |
| Authors | |
| Primary citation | 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 Cited by 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: 39521150DOI: 10.1016/j.bmcl.2024.130007 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.75 Å) |
Structure validation
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