6wk1

SETD3 in Complex with an Actin Peptide with His73 Replaced with Methionine

spinqualitylabelsall models 6wk1, resolution 1.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6wk1 is a 4 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 1.89Å Ligands: ACT, EDO, GOL, SAH Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease ACTG_HUMAN Baraitser-Winter syndrome;Autosomal dominant non-syndromic sensorineural deafness type DFNA. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function ACTG_HUMAN Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. Publication Abstract from PubMed Most characterized protein methylation events encompass arginine and lysine N-methylation, and only a few cases of protein methionine thiomethylation have been reported. Newly discovered oncohistone mutations include lysine-to-methionine substitutions at positions 27 and 36 of histone H3.3. In these instances, the methionine substitution localizes to the active-site pocket of the corresponding histone lysine methyltransferase, thereby inhibiting the respective transmethylation activity. SET domain-containing 3 (SETD3) is a protein (i.e. actin) histidine methyltransferase. Here, we generated an actin variant in which the histidine target of SETD3 was substituted with methionine. As for previously characterized histone SET domain proteins, the methionine substitution substantially (76-fold) increased binding affinity for SETD3 and inhibited SETD3 activity on histidine. Unexpectedly, SETD3 was active on the substituted methionine, generating S-methylmethionine in the context of actin peptide. The ternary structure of SETD3 in complex with the methionine-containing actin peptide at 1.9 A resolution revealed that the hydrophobic thioether side chain is packed by the aromatic rings of Tyr312 and Trp273 as well as the hydrocarbon side chain of Ile310. Our results suggest that placing methionine properly in the active site-within close proximity to and in line with the incoming methyl group of SAM-would allow some SET domain proteins to selectively methylate methionine in proteins. Characterization of SETD3 methyltransferase mediated protein methionine methylation.,Dai S, Holt MV, Horton JR, Woodcock CB, Patel A, Zhang X, Young NL, Wilkinson AW, Cheng X J Biol Chem. 2020 Jun 5. pii: RA120.014072. doi: 10.1074/jbc.RA120.014072. PMID:32503840 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone methyltransferase 3D structures

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