5eg2

SET7/9 N265A in complex with AdoHcy and TAF10 peptide

spinqualitylabelsall models 5eg2, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5eg2 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NA, SAH NonStd Res: MLZ Activity: Histone-lysine N-methyltransferase, with EC number 2.1.1.43 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [SETD7_HUMAN] Histone methyltransferase that specifically monomethylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Plays a central role in the transcriptional activation of genes such as collagenase or insulin. Recruited by IPF1/PDX-1 to the insulin promoter, leading to activate transcription. Has also methyltransferase activity toward non-histone proteins such as p53/TP53, TAF10, and possibly TAF7 by recognizing and binding the [KR]-[STA]-K in substrate proteins. Monomethylates 'Lys-189' of TAF10, leading to increase the affinity of TAF10 for RNA polymerase II. Monomethylates 'Lys-372' of p53/TP53, stabilizing p53/TP53 and increasing p53/TP53-mediated transcriptional activation. [TAF10_HUMAN] TAFs are components of the transcription factor IID (TFIID) complex, PCAF histone acetylase complex and TBP-free TAFII complex (TFTC). TIIFD is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. Publication Abstract from PubMed Recent studies have demonstrated that carbon-oxygen (CH...O) hydrogen bonds have important roles in S-adenosylmethionine (AdoMet) recognition and catalysis in methyltransferases. Here, we investigate noncovalent interactions that occur between the AdoMet sulfur cation and oxygen atoms in methyltransferase active sites. These interactions represent sulfur-oxygen (S...O) chalcogen bonds in which the oxygen atom donates a lone pair of electrons to the sigma antibonding orbital of the AdoMet sulfur atom. Structural, biochemical, and computational analyses of an asparagine mutation in the lysine methyltransferase SET7/9 that abolishes AdoMet S...O chalcogen bonding reveal that this interaction enhances substrate binding affinity relative to the product S-adenosylhomocysteine. Corroborative quantum mechanical calculations demonstrate that sulfonium systems form strong S...O chalcogen bonds relative to their neutral thioether counterparts. An inspection of high-resolution crystal structures reveals the presence of AdoMet S...O chalcogen bonding in different classes of methyltransferases, illustrating that these interactions are not limited to SET domain methyltransferases. Together, these results demonstrate that S...O chalcogen bonds contribute to AdoMet recognition and can enable methyltransferases to distinguish between substrate and product. Sulfur-Oxygen Chalcogen Bonding Mediates AdoMet Recognition in the Lysine Methyltransferase SET7/9.,Fick RJ, Kroner GM, Nepal B, Magnani R, Horowitz S, Houtz RL, Scheiner S, Trievel RC ACS Chem Biol. 2016 Jan 12. PMID:26713889 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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