5jsj | pdb_00005jsj

Crystal structure of Spindlin1 bound to compound EML631

spinqualitylabelsall models 5jsj, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5jsj is a 2 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 2.348Å Ligands: 6PD, CL, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SPIN1_HUMAN May play a role in cell-cycle regulation during the transition from gamete to embryo (By similarity). Publication Abstract from PubMed The discovery of inhibitors of methyl- and acetyl-binding domains has provided evidence for the 'druggability' of epigenetic effector molecules. The small-molecule probe UNC1215 prevents methyl-dependent protein-protein interactions by engaging the aromatic cage of MBT domains and, with lower affinity, Tudor domains. Using a library of tagged UNC1215 analogs, we screened a protein-domain microarray of human methyllysine effector molecules to rapidly detect compounds with new binding profiles with either increased or decreased specificity. Using this approach, we identified a compound (EML405) that acquired a novel interaction with the Tudor-domain-containing protein Spindlin1 (SPIN1). Structural studies facilitated the rational synthesis of SPIN1 inhibitors with increased selectivity (EML631-633), which engage SPIN1 in cells, block its ability to 'read' H3K4me3 marks and inhibit its transcriptional-coactivator activity. Protein microarrays can thus be used as a platform to 'target-hop' and identify small molecules that bind and compete with domain-motif interactions. Developing Spindlin1 small-molecule inhibitors by using protein microarrays.,Bae N, Viviano M, Su X, Lv J, Cheng D, Sagum C, Castellano S, Bai X, Johnson C, Khalil MI, Shen J, Chen K, Li H, Sbardella G, Bedford MT Nat Chem Biol. 2017 Jul;13(7):750-756. doi: 10.1038/nchembio.2377. Epub 2017 May , 15. PMID:28504676 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Spindlin

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