7z5r

Structure of the mouse 8-oxoguanine DNA Glycosylase mOGG1 in complex with ligand TH012035

spinqualitylabelsall models 7z5r, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7z5r is a 3 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: IGQ, NI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function OGG1_MOUSE DNA repair enzyme that incises DNA at 8-oxoG residues. Excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine (FAPY) from damaged DNA. Has a beta-lyase activity that nicks DNA 3' to the lesion. Publication Abstract from PubMed Fragment-based screening can catalyze drug discovery by identifying novel scaffolds, but this approach is limited by the small chemical libraries studied by biophysical experiments and the challenging optimization process. To expand the explored chemical space, we employ structure-based docking to evaluate orders-of-magnitude larger libraries than those used in traditional fragment screening. We computationally dock a set of 14 million fragments to 8-oxoguanine DNA glycosylase (OGG1), a difficult drug target involved in cancer and inflammation, and evaluate 29 highly ranked compounds experimentally. Four of these bind to OGG1 and X-ray crystallography confirms the binding modes predicted by docking. Furthermore, we show how fragment elaboration using searches among billions of readily synthesizable compounds identifies submicromolar inhibitors with anti-inflammatory and anti-cancer effects in cells. Comparisons of virtual screening strategies to explore a chemical space of 10(22) compounds illustrate that fragment-based design enables enumeration of all molecules relevant for inhibitor discovery. Virtual fragment screening is hence a highly efficient strategy for navigating the rapidly growing combinatorial libraries and can serve as a powerful tool to accelerate drug discovery efforts for challenging therapeutic targets. Virtual fragment screening for DNA repair inhibitors in vast chemical space.,Luttens A, Vo DD, Scaletti ER, Wiita E, Almlof I, Wallner O, Davies J, Kosenina S, Meng L, Long M, Mortusewicz O, Masuyer G, Ballante F, Michel M, Homan E, Scobie M, Kalderen C, Warpman Berglund U, Tarnovskiy AV, Radchenko DS, Moroz YS, Kihlberg J, Stenmark P, Helleday T, Carlsson J Nat Commun. 2025 Feb 18;16(1):1741. doi: 10.1038/s41467-025-56893-9. PMID:39966348 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine/threonine protein kinase 3D structures

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