3to6

Crystal structure of yeast Esa1 HAT domain complexed with H4K16CoA bisubstrate inhibitor

spinqualitylabelsall models 3to6, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3to6 is a 2 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: ALY, CMC Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ESA1_YEAST Catalytic component of the NuA4 histone acetyltransferase (HAT) complex which is involved in epigenetic transcriptional activation of selected genes principally by acetylation of nucleosomal histones H4, H3, H2B, H2A and H2A variant H2A.Z. Acetylates histone H4 to form H4K5ac, H4K8ac, H4K12ac and H4K16ac, histone H3 to form H3K14ac, histone H2B to form H2BK16ac, histone H2A to form H2AK4ac and H2AK7ac, and histone variant H2A.Z to form H2A.ZK14ac. Acetylation of histone H4 is essential for DNA double-strand break repair through homologous recombination. Involved in cell cycle progression. Recruitment to promoters depends on H3K4me. Publication Abstract from PubMed The MYST protein lysine acetyltransferases are evolutionarily conserved throughout eukaryotes and acetylate proteins to regulate diverse biological processes including gene regulation, DNA repair, cell-cycle regulation, stem cell homeostasis and development. Here, we demonstrate that MYST protein acetyltransferase activity requires active site lysine autoacetylation. The X-ray crystal structures of yeast Esa1 (yEsa1/KAT5) bound to a bisubstrate H4K16CoA inhibitor and human MOF (hMOF/KAT8/MYST1) reveal that they are autoacetylated at a strictly conserved lysine residue in MYST proteins (yEsa1-K262 and hMOF-K274) in the enzyme active site. The structure of hMOF also shows partial occupancy of K274 in the unacetylated form, revealing that the side chain reorients to a position that engages the catalytic glutamate residue and would block cognate protein substrate binding. Consistent with the structural findings, we present mass spectrometry data and biochemical experiments to demonstrate that this lysine autoacetylation on yEsa1, hMOF and its yeast orthologue, ySas2 (KAT8) occurs in solution and is required for acetylation and protein substrate binding in vitro. We also show that this autoacetylation occurs in vivo and is required for the cellular functions of these MYST proteins. These findings provide an avenue for the autoposttranslational regulation of MYST proteins that is distinct from other acetyltransferases but draws similarities to the phosphoregulation of protein kinases. MYST protein acetyltransferase activity requires active site lysine autoacetylation.,Yuan H, Rossetto D, Mellert H, Dang W, Srinivasan M, Johnson J, Hodawadekar S, Ding EC, Speicher K, Abshiru N, Perry R, Wu J, Yang C, Zheng YG, Speicher DW, Thibault P, Verreault A, Johnson FB, Berger SL, Sternglanz R, McMahon SB, Cote J, Marmorstein R EMBO J. 2011 Oct 21. doi: 10.1038/emboj.2011.382. PMID:22020126 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone acetyltransferase 3D structures

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