9FNU
Structure of the mouse 8-oxoguanine DNA Glycosylase mOGG1 in complex with ligand TH13579
This is a non-PDB format compatible entry.
Summary for 9FNU
| Entry DOI | 10.2210/pdb9fnu/pdb |
| Descriptor | N-glycosylase/DNA lyase, 3-(2-azanylethyl)-2-pyridin-3-yl-1~{H}-indol-5-ol, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | complex, dna binding protein |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 3 |
| Total formula weight | 108360.64 |
| Authors | Scaletti, E.,Stenmark, P. (deposition date: 2024-06-11, release date: 2025-06-25, Last modification date: 2025-11-26) |
| Primary citation | Varga, M.,Ortis, F.,Del Prado, A.,Eddershaw, A.,Scaletti Hutchinson, E.,Hank, E.C.,Zhou, K.,Rudolfova, N.,Dodaro, A.,Wiita, E.,Almlof, I.,Karsten, S.,Mamonov, K.,Ahmed, S.H.,Bentley, K.,Wallner, O.,Homan, E.J.,Scobie, M.,Helleday, T.,Prejano, M.,Stenmark, P.,de Vega, M.,Watson, A.J.B.,Michel, M. Giving an Enzyme Scissors: Serotonin Derivatives as Potent Organocatalytic Switches for DNA Repair Enzyme OGG1. J.Med.Chem., 68:22455-22483, 2025 Cited by PubMed Abstract: The base excision repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1) plays a central role in maintaining genome integrity and mediating cellular responses to oxidative stress. As such, it represents an attractive target for pharmaceutical modulation. Small-molecule organocatalytic switches (ORCAs) greatly enhance the rate of OGG1-catalyzed cleavage of DNA abasic sites, thereby accelerating DNA repair. Here, we present the discovery and hit-to-lead optimization of a novel class of highly potent serotonin-derived ORCAs with greatly improved pharmacokinetic properties. Biochemical assays, X-ray crystallography, and molecular dynamics simulations point toward a water-mediated mechanism of activation, distinct from previously proposed Brønsted base-assisted models. These findings establish serotonin-based ORCAs as promising chemical probes and potential leads for therapeutic modulation of OGG1 in oxidative stress-driven diseases. PubMed: 41092057DOI: 10.1021/acs.jmedchem.5c01454 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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