7nto | pdb_00007nto

The structure of RRM domain of human TRMT2A at 1.23 A resolution

spinqualitylabelsall models 7nto, resolution 1.23Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7nto is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.23Å Ligands: CL, EDO, NA, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TRM2A_HUMAN May be involved in nucleic acid metabolism and/or modifications. Publication Abstract from PubMed Polyglutamine (polyQ) diseases are characterized by an expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats encoding for an uninterrupted prolonged polyQ tract. We previously identified TRMT2A as a strong modifier of polyQ-induced toxicity in an unbiased large-scale screen in Drosophila melanogaster. This work aimed at identifying and validating pharmacological TRMT2A inhibitors as treatment opportunities for polyQ diseases in humans. Computer-aided drug discovery was implemented to identify human TRMT2A inhibitors. Additionally, the crystal structure of one protein domain, the RNA recognition motif (RRM), was determined, and Biacore experiments with the RRM were performed. The identified molecules were validated for their potency to reduce polyQ aggregation and polyQ-induced cell death in human HEK293T cells and patient derived fibroblasts. Our work provides a first step towards pharmacological inhibition of this enzyme and indicates TRMT2A as a viable drug target for polyQ diseases. Small-molecule modulators of TRMT2A decrease PolyQ aggregation and PolyQ-induced cell death.,Margreiter MA, Witzenberger M, Wasser Y, Davydova E, Janowski R, Metz J, Habib P, Sahnoun SEM, Sobisch C, Poma B, Palomino-Hernandez O, Wagner M, Carell T, Jon Shah N, Schulz JB, Niessing D, Voigt A, Rossetti G Comput Struct Biotechnol J. 2021 Dec 28;20:443-458. doi:, 10.1016/j.csbj.2021.12.029. eCollection 2022. PMID:35070167 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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