6mon | pdb_00006mon

Crystal structure of human SMYD2 in complex with Nle-peptide inhibitor

spinqualitylabelsall models 6mon, resolution 2.71Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6mon is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.711Å Ligands: GOL, NLE, SAH, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SMYD2_HUMAN Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins. Specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). Has also methyltransferase activity toward non-histone proteins such as p53/TP53 and RB1. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates 'Lys-860' of RB1/RB. Publication Abstract from PubMed Lysine methylation is a key regulator of histone protein function. Beyond histones, few connections have been made to the enzymes responsible for the deposition of these posttranslational modifications. Here, we debut a high-throughput functional proteomics platform that maps the sequence determinants of lysine methyltransferase (KMT) substrate selectivity without a priori knowledge of a substrate or target proteome. We demonstrate the predictive power of this approach for identifying KMT substrates, generating scaffolds for inhibitor design, and predicting the impact of missense mutations on lysine methylation signaling. By comparing KMT selectivity profiles to available lysine methylome datasets, we reveal a disconnect between preferred KMT substrates and the ability to detect these motifs using standard mass spectrometry pipelines. Collectively, our studies validate the use of this platform for guiding the study of lysine methylation signaling and suggest that substantial gaps exist in proteome-wide curation of lysine methylomes. A functional proteomics platform to reveal the sequence determinants of lysine methyltransferase substrate selectivity.,Cornett EM, Dickson BM, Krajewski K, Spellmon N, Umstead A, Vaughan RM, Shaw KM, Versluis PP, Cowles MW, Brunzelle J, Yang Z, Vega IE, Sun ZW, Rothbart SB Sci Adv. 2018 Nov 28;4(11):eaav2623. doi: 10.1126/sciadv.aav2623. eCollection, 2018 Nov. PMID:30498785 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone methyltransferase 3D structures

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