8JTN

Tudor domain of TDRD3 in complex with a small molecule

Summary for 8JTN

• Entry DOI: 10.2210/pdb8jtn/pdb
• Descriptor: Tudor domain-containing protein 3, 2-propyl-2-azoniatricyclo[7.3.0.0^{3,7}]dodeca-1(9),2,7-trien-8-amine (3 entities in total)
• Functional Keywords: inhibitors, complexes, tudo domains, histone readers, gene expression regulation, gene regulation
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 7392.61

Authors

Chen, M.,Wang, Z.,Li, W.,Shang, X.,Liu, Y. (deposition date: 2023-06-22, release date: 2023-08-09, Last modification date: 2024-05-29)

Primary citation

Chen, M.,Wang, Z.,Li, W.,Chen, Y.,Xiao, Q.,Shang, X.,Huang, X.,Wei, Z.,Ji, X.,Liu, Y.
Crystal structure of Tudor domain of TDRD3 in complex with a small molecule antagonist.
Biochim Biophys Acta Gene Regul Mech, 1866:194962-194962, 2023

PubMed Abstract: 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.

PubMed: 37499935
DOI: 10.1016/j.bbagrm.2023.194962

Experimental method

X-RAY DIFFRACTION (1.8 Å)