8jtn | pdb_00008jtn

Tudor domain of TDRD3 in complex with a small molecule

spinqualitylabelsall models 8jtn, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8jtn 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 1.8Å Ligands: F5W Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TDRD3_HUMAN Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. In nucleus, acts as a coactivator: recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci. In cytoplasm, may play a role in the assembly and/or disassembly of mRNA stress granules and in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins. Publication Abstract from PubMed Tudor domain-containing protein 3 (TDRD3) is involved in regulating transcription and translation, promoting breast cancer progression, and modulating neurodevelopment and mental health, making it a promising therapeutic target for associated diseases. The Tudor domain of TDRD3 is essential for its biological functions, and targeting this domain with potent and selective chemical probes may modulate its engagement with chromatin and related functions. Here we reported a study of TDRD3 antagonist following on our earlier work on the development of the SMN antagonist, Compound 1, and demonstrated that TDRD3 can bind effectively to Compound 2, a triple-ring analog of Compound 1. Our structural analysis suggested that the triple-ring compound bound better to TDRD3 due to its smaller side chain at Y566 compared to W102 in SMN. We also revealed that adding a small hydrophobic group to the N-methyl site of Compound 1 can improve binding. These findings provide a path for identifying antagonists for single canonical Tudor domain-containing proteins such as TDRD3 and SMN. Crystal structure of Tudor domain of TDRD3 in complex with a small molecule antagonist.,Chen M, Wang Z, Li W, Chen Y, Xiao Q, Shang X, Huang X, Wei Z, Ji X, Liu Y Biochim Biophys Acta Gene Regul Mech. 2023 Sep;1866(3):194962. doi: , 10.1016/j.bbagrm.2023.194962. Epub 2023 Jul 25. PMID:37499935 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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