登録情報 データベース : EMDB / ID : EMD-28915 ダウンロードとリンクタイトル SIRT6 bound to an H3K9Ac nucleosome マップデータmap A 詳細 試料複合体 : SIRT6 bound to H3K9Acタンパク質・ペプチド : Histone H3.2タンパク質・ペプチド : Histone H4タンパク質・ペプチド : Histone H2A type 1タンパク質・ペプチド : Histone H2BDNA : DNA (148-MER)DNA : DNA (148-MER)タンパク質・ペプチド : NAD-dependent protein deacylase sirtuin-6 残り3件を表示 表示を減らすリガンド : [(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl [(3aR,5R,6R,6aR)-6-hydroxytetrahydro-2H-furo[2,3-d][1,3]oxathiol-5-yl]methyl dihydrogen diphosphate (non-preferred name)リガンド : ZINC ION 詳細 キーワード nucleosome / SIRTUIN6 / histone deacylation / H3K9Ac / GENE REGULATION機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
histone H3K56 deacetylase activity, NAD-dependent / histone H3K18 deacetylase activity, NAD-dependent / ketone biosynthetic process / histone H3K9 deacetylase activity, hydrolytic mechanism / histone H3K9 deacetylase activity, NAD-dependent / protein delipidation / NAD+-protein-lysine ADP-ribosyltransferase activity / regulation of lipid catabolic process / chromosome, subtelomeric region / positive regulation of protein localization to chromatin ... histone H3K56 deacetylase activity, NAD-dependent / histone H3K18 deacetylase activity, NAD-dependent / ketone biosynthetic process / histone H3K9 deacetylase activity, hydrolytic mechanism / histone H3K9 deacetylase activity, NAD-dependent / protein delipidation / NAD+-protein-lysine ADP-ribosyltransferase activity / regulation of lipid catabolic process / chromosome, subtelomeric region / positive regulation of protein localization to chromatin / NAD+-protein-arginine ADP-ribosyltransferase activity / DNA damage sensor activity / NAD-dependent protein demyristoylase activity / NAD-dependent protein depalmitoylase activity / positive regulation of stem cell differentiation / negative regulation of D-glucose import / positive regulation of chondrocyte proliferation / NAD-dependent protein lysine deacetylase activity / transposable element silencing / cardiac muscle cell differentiation / protein acetyllysine N-acetyltransferase / pericentric heterochromatin formation / protein deacetylation / histone deacetylase activity, NAD-dependent / protein localization to site of double-strand break / positive regulation of blood vessel branching / negative regulation of glycolytic process / negative regulation of protein localization to chromatin / TORC2 complex binding / positive regulation of vascular endothelial cell proliferation / histone deacetylase regulator activity / regulation of double-strand break repair via homologous recombination / positive regulation of double-strand break repair / negative regulation of protein import into nucleus / regulation of protein secretion / lncRNA binding / negative regulation of gene expression, epigenetic / DNA repair-dependent chromatin remodeling / positive regulation of stem cell proliferation / positive regulation of stem cell population maintenance / NAD+-protein mono-ADP-ribosyltransferase activity / positive regulation of telomere maintenance / pericentric heterochromatin / regulation of lipid metabolic process / site of DNA damage / NAD+ poly-ADP-ribosyltransferase activity / negative regulation of transcription elongation by RNA polymerase II / negative regulation of cellular senescence / 転移酵素; グリコシル基を移すもの; 五炭糖残基を移すもの / NAD+ binding / positive regulation of fat cell differentiation / negative regulation of gluconeogenesis / subtelomeric heterochromatin formation / regulation of protein localization to plasma membrane / response to UV / nucleosome binding / enzyme regulator activity / 転移酵素; アシル基を移すもの; アミノアシル基以外のアシル基を移すもの / nucleotidyltransferase activity / positive regulation of protein export from nucleus / determination of adult lifespan / circadian regulation of gene expression / chromatin DNA binding / regulation of circadian rhythm / protein destabilization / base-excision repair / positive regulation of insulin secretion / Pre-NOTCH Transcription and Translation / positive regulation of fibroblast proliferation / protein import into nucleus / structural constituent of chromatin / transcription corepressor activity / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / glucose homeostasis / nucleosome / site of double-strand break / heterochromatin formation / double-strand break repair / nucleosome assembly / Processing of DNA double-strand break ends / positive regulation of cold-induced thermogenesis / damaged DNA binding / chromatin remodeling / protein heterodimerization activity / negative regulation of cell population proliferation / intracellular membrane-bounded organelle / chromatin binding / chromatin / endoplasmic reticulum / negative regulation of transcription by RNA polymerase II / protein homodimerization activity / DNA binding / zinc ion binding / nucleoplasm / nucleus 類似検索 - 分子機能 Sirtuin family / : / Sir2 family / Sirtuin family, catalytic core domain / Sirtuin catalytic domain profile. / DHS-like NAD/FAD-binding domain superfamily / : / Histone H2B signature. / Histone H2A conserved site / Histone H2A signature. ... Sirtuin family / : / Sir2 family / Sirtuin family, catalytic core domain / Sirtuin catalytic domain profile. / DHS-like NAD/FAD-binding domain superfamily / : / Histone H2B signature. / Histone H2A conserved site / Histone H2A signature. / Histone H2B / Histone H2B / Histone H2A, C-terminal domain / C-terminus of histone H2A / Histone 2A / Histone H2A / TATA box binding protein associated factor / TATA box binding protein associated factor (TAF), histone-like fold domain / Histone H4, conserved site / Histone H4 signature. / Histone H4 / Histone H4 / CENP-T/Histone H4, histone fold / Centromere kinetochore component CENP-T histone fold / Histone H3 signature 1. / Histone H3 signature 2. / Histone H3 / Histone H3/CENP-A / Histone H2A/H2B/H3 / Core histone H2A/H2B/H3/H4 / Histone-fold 類似検索 - ドメイン・相同性 Histone H2B 1.1 / Histone H2A type 1 / Histone H4 / Histone H3.2 / NAD-dependent protein deacylase sirtuin-6 類似検索 - 構成要素生物種 Xenopus laevis (アフリカツメガエル) / Homo sapiens (ヒト) / synthetic construct (人工物) 手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.1 Å 詳細 データ登録者Markert J / Whedon S / Wang Z / Cole P / Farnung L 資金援助 1件 詳細 詳細を隠すOrganization Grant number 国 Not funded
引用ジャーナル : J Am Chem Soc / 年 : 2023タイトル : Structural Basis of Sirtuin 6-Catalyzed Nucleosome Deacetylation.著者 : Zhipeng A Wang / Jonathan W Markert / Samuel D Whedon / Maheeshi Yapa Abeywardana / Kwangwoon Lee / Hanjie Jiang / Carolay Suarez / Hening Lin / Lucas Farnung / Philip A Cole / 要旨 : The reversible acetylation of histone lysine residues is controlled by the action of acetyltransferases and deacetylases (HDACs), which regulate chromatin structure and gene expression. The sirtuins ... The reversible acetylation of histone lysine residues is controlled by the action of acetyltransferases and deacetylases (HDACs), which regulate chromatin structure and gene expression. The sirtuins are a family of NAD-dependent HDAC enzymes, and one member, sirtuin 6 (Sirt6), influences DNA repair, transcription, and aging. Here, we demonstrate that Sirt6 is efficient at deacetylating several histone H3 acetylation sites, including its canonical site Lys9, in the context of nucleosomes but not free acetylated histone H3 protein substrates. By installing a chemical warhead at the Lys9 position of histone H3, we trap a catalytically poised Sirt6 in complex with a nucleosome and employ this in cryo-EM structural analysis. The structure of Sirt6 bound to a nucleosome reveals extensive interactions between distinct segments of Sirt6 and the H2A/H2B acidic patch and nucleosomal DNA, which accounts for the rapid deacetylation of nucleosomal H3 sites and the disfavoring of histone H2B acetylation sites. These findings provide a new framework for understanding how HDACs target and regulate chromatin. 履歴 登録 2022年11月21日 - ヘッダ(付随情報) 公開 2023年4月5日 - マップ公開 2023年4月5日 - 更新 2025年5月21日 - 現状 2025年5月21日 処理サイト : RCSB / 状態 : 公開
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