7w28

Crystal Structure of SETD3-SAH in complex with betaA-4PyrAla73 peptide

spinqualitylabelsall models 7w28, resolution 1.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7w28 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 1.79Å Ligands: N9P, SAH, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SETD3_HUMAN Histone methyltransferase that methylates 'Lys-36' of histone H3 (H3K36me). H3 'Lys-36' methylation represents a specific tag for epigenetic transcriptional activation (By similarity). Publication Abstract from PubMed Actin histidine N(tau) -methylation by histidine methyltransferase SETD3 plays an important role in human biology and diseases. Here, we report integrated synthetic, biocatalytic, biostructural, and computational analyses on human SETD3-catalyzed methylation of actin peptides possessing histidine and its structurally and chemically diverse mimics. Our enzyme assays supported by biostructural analyses demonstrate that SETD3 has a broader substrate scope beyond histidine, including N-nucleophiles on the aromatic and aliphatic side chains. Quantum mechanical/molecular mechanical molecular dynamics and free-energy simulations provide insight into binding geometries and the free energy barrier for the enzymatic methyl transfer to histidine mimics, further supporting experimental data that histidine is the superior SETD3 substrate over its analogs. This work demonstrates that human SETD3 has a potential to catalyze efficient methylation of several histidine mimics, overall providing mechanistic, biocatalytic, and functional insight into actin histidine methylation by SETD3. Histidine methyltransferase SETD3 methylates structurally diverse histidine mimics in actin.,Hintzen JCJ, Ma H, Deng H, Witecka A, Andersen SB, Drozak J, Guo H, Qian P, Li H, Mecinovic J Protein Sci. 2022 May;31(5):e4305. doi: 10.1002/pro.4305. PMID:35481649 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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