2kgp | pdb_00002kgp

Structural basis for stabilization of the tau pre-mRNA splicing regulatory element by Novantrone (Mitoxantrone)

spinqualitylabelsall models 2kgp, 10 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2kgp is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MIX Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Some familial neurodegenerative diseases are associated with mutations that destabilize a putative stem-loop structure within an intronic region of the tau pre-messenger RNA (mRNA) and alter the production of tau protein isoforms by alternative splicing. Because stabilization of the stem loop reverses the splicing pattern associated with neurodegeneration, small molecules that stabilize this stem loop would provide new ways to dissect the mechanism of neurodegeneration and treat tauopathies. The anticancer drug mitoxantrone was recently identified in a high throughput screen to stabilize the tau pre-mRNA stem loop. Here we report the solution structure of the tau mRNA-mitoxantrone complex, validated by the structure-activity relationship of existing mitoxantrone analogs. The structure describes the molecular basis for their interaction with RNA and provides a rational basis to optimize the activity of this new class of RNA-binding molecules. Structural basis for stabilization of the tau pre-mRNA splicing regulatory element by novantrone (mitoxantrone).,Zheng S, Chen Y, Donahue CP, Wolfe MS, Varani G Chem Biol. 2009 May 29;16(5):557-66. PMID:19477420 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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