EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Molecular basis for acetyl-CoA production by ATP-citrate lyase.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 27, Issue 1, Page 33-41, Year 2020
掲載日	2019年12月23日
著者	Xuepeng Wei / Kollin Schultz / Gleb A Bazilevsky / Austin Vogt / Ronen Marmorstein /
PubMed 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.
リンク	Nat Struct Mol Biol / PubMed:31873304 / PubMed Central
手法	EM (単粒子)
解像度	2.85 - 4.3 Å
構造データ	20413 6poe EMDB-20413, PDB-6poe: Structure of ACLY in complex with CoA 手法: EM (単粒子) / 解像度: 3.5 Å 20414 6pof EMDB-20414, PDB-6pof: Structure of human ATP citrate lyase 手法: EM (単粒子) / 解像度: 4.3 Å 20783 6ui9 EMDB-20783, PDB-6ui9: Structure of human ATP citrate lyase in complex with acetyl-CoA and oxaloacetate 手法: EM (単粒子) / 解像度: 3.1 Å 20784 6uia EMDB-20784, PDB-6uia: Structure of ATP citrate lyase with CoA in a partially open conformation 手法: EM (単粒子) / 解像度: 4.3 Å 20902 6uuw EMDB-20902, PDB-6uuw: Structure of human ATP citrate lyase E599Q mutant in complex with Mg2+, citrate, ATP and CoA 手法: EM (単粒子) / 解像度: 2.85 Å 20903 6uuz EMDB-20903, PDB-6uuz: Structure of ACLY in the presence of citrate and CoA 手法: EM (単粒子) / 解像度: 3.0 Å 20904 6uv5 EMDB-20904, PDB-6uv5: Structure of human ATP citrate lyase in complex with acetyl-CoA and oxaloacetate 手法: EM (単粒子) / 解像度: 3.4 Å
化合物	ChemComp-COA: COENZYME A / CoA ChemComp-HOH: WATER ChemComp-ACO: ACETYL COENZYME A / アデノシン3′-りん酸5′-[二りん酸P²-[(R)-3-ヒドロキシ-2,2-ジメチル-3-[[(以下略) ChemComp-OAA: OXALOACETATE ION ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子YM ChemComp-Y2A: (2S)-2-hydroxy-2-[2-oxo-2-(phosphonooxy)ethyl]butanedioic acid 化合物画像なし ChemComp-UNL: Unknown ligand
由来	homo sapiens (ヒト)
キーワード	LYASE / apo / open conformation / enzyme