| http://purl.uniprot.org/citations/29645362 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29645362 | http://www.w3.org/2000/01/rdf-schema#comment | "As a reader of di-methylated arginine on various proteins, such as histone, RNA polymerase II, PIWI and Fragile X mental retardation protein, the Tudor domain of Tudor domain-containing protein 3 (TDRD3) mediates transcriptional activation in nucleus and formation of stress granules in the cytoplasm. Despite the TDRD3 implication in cancer cell proliferation and invasion, warheads to block the di-methylated arginine recognition pocket of the TDRD3 Tudor domain have not yet been uncovered. Here we identified 14 small molecule hits against the TDRD3 Tudor domain through NMR fragment-based screening. These hits were further cross-validated by using competitive fluorescence polarization and isothermal titration calorimetry experiments. The crystal structure of the TDRD3 Tudor domain in complex with hit 1 reveals a distinct binding mode from the nature substrate. Hit 1 protrudes into the aromatic cage of the TDRD3 Tudor domain, where the aromatic residues are tilted to accommodate a sandwich-like π-π interaction. The side chain of the conserved residue N596 swings away 3.1 Å to form a direct hydrogen bond with hit 1. Moreover, this compound shows a decreased affinity against the single Tudor domain of survival motor neuron protein, but no detectable binding to neither the tandem Tudor domain of TP53-binding protein 1 nor the extended Tudor domain of staphylococcal nuclease domain-containing protein 1. Our work depicts the structural plasticity of the TDRD3 Tudor domain and paves the way for the subsequent structure-guided discovery of selective inhibitors targeting Tudor domains.DatabaseStructural data are available in the PDB under the accession number 5YJ8."xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.org/dc/terms/identifier | "doi:10.1111/febs.14469"xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/author | "Gao J."xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/author | "Li F."xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/author | "Liu J."xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/author | "Liu M."xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/author | "Wu J."xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/author | "Zhang J."xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/author | "Zhang S."xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/author | "Yang Y."xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/author | "Ma R."xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/author | "Ruan K."xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/author | "Nshogoza G."xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/name | "FEBS J"xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/pages | "2091-2103"xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/title | "Structural plasticity of the TDRD3 Tudor domain probed by a fragment screening hit."xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://purl.uniprot.org/core/volume | "285"xsd:string |
| http://purl.uniprot.org/citations/29645362 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/29645362 |
| http://purl.uniprot.org/citations/29645362 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/29645362 |
| http://purl.uniprot.org/uniprot/#_Q9H7E2-mappedCitation-29645362 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29645362 |
| http://purl.uniprot.org/uniprot/Q9H7E2 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/29645362 |