登録情報 データベース : PDB / ID : 6ui9 構造の表示 ダウンロードとリンクタイトル Structure of human ATP citrate lyase in complex with acetyl-CoA and oxaloacetate 要素ACLY 詳細 キーワード LYASE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
ATP citrate synthase activity / ATP citrate synthase / Fatty acyl-CoA biosynthesis / citrate metabolic process / ChREBP activates metabolic gene expression / acetyl-CoA biosynthetic process / oxaloacetate metabolic process / coenzyme A metabolic process / lipid biosynthetic process / cholesterol biosynthetic process ... ATP citrate synthase activity / ATP citrate synthase / Fatty acyl-CoA biosynthesis / citrate metabolic process / ChREBP activates metabolic gene expression / acetyl-CoA biosynthetic process / oxaloacetate metabolic process / coenzyme A metabolic process / lipid biosynthetic process / cholesterol biosynthetic process / tricarboxylic acid cycle / fatty acid biosynthetic process / azurophil granule lumen / ficolin-1-rich granule lumen / Neutrophil degranulation / extracellular exosome / extracellular region / nucleoplasm / ATP binding / membrane / metal ion binding / cytosol 類似検索 - 分子機能 ATP-citrate synthase / ATP-citrate synthase, citrate-binding domain / ATP citrate lyase citrate-binding / ATP-citrate lyase/succinyl-CoA ligase, active site / ATP-citrate lyase/succinyl-CoA ligase, conserved site / ATP-citrate lyase / succinyl-CoA ligases family active site. / ATP-citrate lyase / succinyl-CoA ligases family signature 1. / Succinyl-CoA synthetase, beta subunit, conserved site / ATP-citrate lyase / succinyl-CoA ligases family signature 3. / ATP-citrate lyase/succinyl-CoA ligase ... ATP-citrate synthase / ATP-citrate synthase, citrate-binding domain / ATP citrate lyase citrate-binding / ATP-citrate lyase/succinyl-CoA ligase, active site / ATP-citrate lyase/succinyl-CoA ligase, conserved site / ATP-citrate lyase / succinyl-CoA ligases family active site. / ATP-citrate lyase / succinyl-CoA ligases family signature 1. / Succinyl-CoA synthetase, beta subunit, conserved site / ATP-citrate lyase / succinyl-CoA ligases family signature 3. / ATP-citrate lyase/succinyl-CoA ligase / CoA-ligase / CoA binding domain / Succinyl-CoA synthetase-like / CoA binding domain / CoA-binding / Citrate synthase / Citrate synthase-like, small alpha subdomain / Citrate synthase superfamily / Citrate synthase, C-terminal domain / NAD(P)-binding domain superfamily 類似検索 - ドメイン・相同性 ACETYL COENZYME *A / OXALOACETATE ION / ATP-citrate synthase 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 電子顕微鏡法 / 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 Wei, X. / Marmorstein, R. 資金援助 米国, 1件 詳細 詳細を隠す組織 認可番号 国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) P01 AG031862 米国
引用ジャーナル : Nat Struct Mol Biol / 年 : 2020タイトル : Molecular basis for acetyl-CoA production by ATP-citrate lyase.著者 : Xuepeng Wei / Kollin Schultz / Gleb A Bazilevsky / Austin Vogt / Ronen Marmorstein / 要旨 : ATP-citrate lyase (ACLY) synthesizes cytosolic acetyl coenzyme A (acetyl-CoA), a fundamental cellular building block. Accordingly, aberrant ACLY activity is observed in many diseases. Here we report ... ATP-citrate lyase (ACLY) synthesizes cytosolic acetyl coenzyme A (acetyl-CoA), a fundamental cellular building block. Accordingly, aberrant ACLY activity is observed in many diseases. Here we report cryo-EM structures of human ACLY, alone or bound to substrates or products. ACLY forms a homotetramer with a rigid citrate synthase homology (CSH) module, flanked by four flexible acetyl-CoA synthetase homology (ASH) domains; CoA is bound at the CSH-ASH interface in mutually exclusive productive or unproductive conformations. The structure of a catalytic mutant of ACLY in the presence of ATP, citrate and CoA substrates reveals a phospho-citryl-CoA intermediate in the ASH domain. ACLY with acetyl-CoA and oxaloacetate products shows the products bound in the ASH domain, with an additional oxaloacetate in the CSH domain, which could function in ACLY autoinhibition. These structures, which are supported by biochemical and biophysical data, challenge previous proposals of the ACLY catalytic mechanism and suggest additional therapeutic possibilities for ACLY-associated metabolic disorders. 履歴 登録 2019年9月30日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2019年12月25日 Provider : repository / タイプ : Initial release改定 1.1 2020年1月1日 Group : Database references / Structure summary / カテゴリ : audit_author / citation / citation_author / Item : _audit_author.name改定 1.2 2020年1月22日 Group : Database references / カテゴリ : citation / citation_authorItem : _citation.journal_volume / _citation.page_first ... _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year / _citation_author.identifier_ORCID 改定 2.0 2021年7月7日 Group : Advisory / Atomic model ... Advisory / Atomic model / Data collection / Database references / Derived calculations / Experimental preparation / Non-polymer description / Refinement description / Source and taxonomy / Structure summary カテゴリ : atom_site / chem_comp ... atom_site / chem_comp / citation / citation_author / em_entity_assembly_naturalsource / em_sample_support / em_software / entity / entity_name_com / entity_src_gen / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_struct_assembly_gen / pdbx_struct_assembly_prop / pdbx_struct_sheet_hbond / pdbx_validate_close_contact / pdbx_validate_peptide_omega / pdbx_validate_rmsd_angle / pdbx_validate_rmsd_bond / pdbx_validate_torsion / refine_ls_restr / software / struct_asym / struct_conf / struct_mon_prot_cis / struct_sheet / struct_sheet_order / struct_sheet_range / struct_site / struct_site_gen Item : _chem_comp.formula / _chem_comp.formula_weight ... _chem_comp.formula / _chem_comp.formula_weight / _chem_comp.id / _chem_comp.mon_nstd_flag / _chem_comp.name / _chem_comp.type / _em_entity_assembly_naturalsource.strain / _em_sample_support.grid_type / _em_software.category / _em_software.fitting_id / _em_software.imaging_id / _em_software.name / _entity_src_gen.gene_src_common_name / _entity_src_gen.pdbx_host_org_ncbi_taxonomy_id / _entity_src_gen.pdbx_host_org_strain / _pdbx_struct_assembly_gen.asym_id_list / _pdbx_struct_assembly_prop.value / _struct_sheet_range.beg_auth_asym_id / _struct_sheet_range.beg_auth_comp_id / _struct_sheet_range.beg_auth_seq_id / _struct_sheet_range.beg_label_asym_id / _struct_sheet_range.beg_label_comp_id / _struct_sheet_range.beg_label_seq_id / _struct_sheet_range.end_auth_asym_id / _struct_sheet_range.end_auth_comp_id / _struct_sheet_range.end_auth_seq_id / _struct_sheet_range.end_label_asym_id / _struct_sheet_range.end_label_comp_id / _struct_sheet_range.end_label_seq_id / _struct_sheet_range.id / _struct_sheet_range.sheet_id 解説 : Ligand geometry / Provider : author / タイプ : Coordinate replacement改定 2.1 2024年3月20日 Group : Data collection / Database references / Refinement descriptionカテゴリ : chem_comp_atom / chem_comp_bond ... chem_comp_atom / chem_comp_bond / database_2 / em_3d_fitting_list / pdbx_initial_refinement_model Item : _database_2.pdbx_DOI / _database_2.pdbx_database_accession ... _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _em_3d_fitting_list.accession_code / _em_3d_fitting_list.initial_refinement_model_id / _em_3d_fitting_list.source_name / _em_3d_fitting_list.type
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