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	Mechanistic insight into allosteric activation of human pyruvate carboxylase by acetyl-CoA.
ジャーナル・号・ページ	Mol Cell, Vol. 82, Issue 21, Page 4116-44130.e6, Year 2022
掲載日	2022年11月3日
著者	Peiwei Chai / Pengfei Lan / Shaobai Li / Deqiang Yao / Chenchen Chang / Mi Cao / Yafeng Shen / Shengfang Ge / Jian Wu / Ming Lei / Xianqun Fan /
PubMed 要旨	Pyruvate carboxylase (PC) catalyzes the two-step carboxylation of pyruvate to produce oxaloacetate, playing a key role in the maintenance of metabolic homeostasis in cells. Given its involvement in ...Pyruvate carboxylase (PC) catalyzes the two-step carboxylation of pyruvate to produce oxaloacetate, playing a key role in the maintenance of metabolic homeostasis in cells. Given its involvement in multiple diseases, PC has been regarded as a potential therapeutic target for obesity, diabetes, and cancer. Albeit acetyl-CoA has been recognized as the allosteric regulator of PC for over 60 years, the underlying mechanism of how acetyl-CoA induces PC activation remains enigmatic. Herein, by using time-resolved cryo-electron microscopy, we have captured the snapshots of PC transitional states during its catalytic cycle. These structures and the biochemical studies reveal that acetyl-CoA stabilizes PC in a catalytically competent conformation, which triggers a cascade of events, including ATP hydrolysis and the long-distance communication between the two reactive centers. These findings provide an integrated picture for PC catalysis and unveil the unique allosteric mechanism of acetyl-CoA in an essential biochemical reaction in all kingdoms of life.
リンク	Mol Cell / PubMed:36283412
手法	EM (単粒子)
解像度	3.3 - 4.0 Å
構造データ	32773 7wta EMDB-32773, PDB-7wta: Cryo-EM structure of human pyruvate carboxylase in apo state 手法: EM (単粒子) / 解像度: 3.9 Å EMDB-32774: PC-(acetyl-CoA) (12.5uM) 手法: EM (単粒子) / 解像度: 3.9 Å 32775 7wtb EMDB-32775, PDB-7wtb: Cryo-EM structure of human pyruvate carboxylase with acetyl-CoA 手法: EM (単粒子) / 解像度: 3.7 Å EMDB-32776: PC-(acetyl-CoA)(50 uM) 手法: EM (単粒子) / 解像度: 3.4 Å EMDB-32777: PC-(acetyl-CoA)(100 uM) 手法: EM (単粒子) / 解像度: 3.6 Å 32778 7wtc EMDB-32778, PDB-7wtc: Cryo-EM structure of human pyruvate carboxylase with acetyl-CoA in the ground state 手法: EM (単粒子) / 解像度: 4.0 Å 32779 7wtd EMDB-32779, PDB-7wtd: Cryo-EM structure of human pyruvate carboxylase with acetyl-CoA in the intermediate state 1 手法: EM (単粒子) / 解像度: 3.9 Å 32780 7wte EMDB-32780, PDB-7wte: Cryo-EM structure of human pyruvate carboxylase with acetyl-CoA in the intermediate state 2 手法: EM (単粒子) / 解像度: 3.3 Å EMDB-32781: Cryo-EM structure of human pyruvate carboxylase with acetyl-CoA in the intermediate state 3 手法: EM (単粒子) / 解像度: 3.9 Å EMDB-32782: Cryo-EM structure of human pyruvate carboxylase with acetyl-CoA in the intermediate state 4 手法: EM (単粒子) / 解像度: 3.9 Å EMDB-32783: Cryo-EM structure of human pyruvate carboxylase with acetyl-CoA in the intermediate state 5 手法: EM (単粒子) / 解像度: 3.8 Å
化合物	ChemComp-BTI: 5-(HEXAHYDRO-2-OXO-1H-THIENO[3,4-D]IMIDAZOL-6-YL)PENTANAL ChemComp-ANP: PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP / AMP-PNP, エネルギー貯蔵分子類似体YM 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-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM ChemComp-COA*: COENZYME A / CoA
由来	homo sapiens (ヒト) human (ヒト)
キーワード	ONCOPROTEIN / pyruvate carboxylase