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	Structural insights into the assembly and substrate selectivity of human SPT-ORMDL3 complex.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 28, Issue 3, Page 249-257, Year 2021
掲載日	2021年2月8日
著者	Sisi Li / Tian Xie / Peng Liu / Lei Wang / Xin Gong /
PubMed 要旨	Human serine palmitoyltransferase (SPT) complex catalyzes the initial and rate-limiting step in the de novo biosynthesis of all sphingolipids. ORMDLs regulate SPT function, with human ORMDL3 being ...Human serine palmitoyltransferase (SPT) complex catalyzes the initial and rate-limiting step in the de novo biosynthesis of all sphingolipids. ORMDLs regulate SPT function, with human ORMDL3 being related to asthma. Here we report three high-resolution cryo-EM structures: the human SPT complex, composed of SPTLC1, SPTLC2 and SPTssa; the SPT-ORMDL3 complex; and the SPT-ORMDL3 complex bound to two substrates, PLP-L-serine (PLS) and a non-reactive palmitoyl-CoA analogue. SPTLC1 and SPTLC2 form a dimer of heterodimers as the catalytic core. SPTssa participates in acyl-CoA coordination, thereby stimulating the SPT activity and regulating the substrate selectivity. ORMDL3 is located in the center of the complex, serving to stabilize the SPT assembly. Our structural and biochemical analyses provide a molecular basis for the assembly and substrate selectivity of the SPT and SPT-ORMDL3 complexes, and lay a foundation for mechanistic understanding of sphingolipid homeostasis and for related therapeutic drug development.
リンク	Nat Struct Mol Biol / PubMed:33558762
手法	EM (単粒子)
解像度	3.2 - 4.0 Å
構造データ	30079 6m4n EMDB-30079, PDB-6m4n: Cryo-EM structure of the dimeric SPT-ORMDL3 complex 手法: EM (単粒子) / 解像度: 3.8 Å 30080 6m4o EMDB-30080, PDB-6m4o: Cryo-EM structure of the monomeric SPT-ORMDL3 complex 手法: EM (単粒子) / 解像度: 3.4 Å EMDB-30081: Cryo-EM map of the dimeric SPT complex 手法: EM (単粒子) / 解像度: 4.0 Å EMDB-30082: Cryo-EM map of the monomeric SPT complex 手法: EM (単粒子) / 解像度: 3.9 Å 30441 7cqi EMDB-30441, PDB-7cqi: Cryo-EM structure of the substrate-bound SPT-ORMDL3 complex 手法: EM (単粒子) / 解像度: 3.2 Å 30442 7cqk EMDB-30442, PDB-7cqk: Cryo-EM structure of the substrate-bound SPT-ORMDL3 complex 手法: EM (単粒子) / 解像度: 3.3 Å
化合物	ChemComp-PLP: PYRIDOXAL-5'-PHOSPHATE / ピリドキサ-ル5′-りん酸 / ピリドキサールリン酸 ChemComp-PLS: [3-HYDROXY-2-METHYL-5-PHOSPHONOOXYMETHYL-PYRIDIN-4-YLMETHYL]-SERINE ChemComp-GE0: [[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-oxidanyl-3-phosphonooxy-oxolan-2-yl]methoxy-oxidanyl-phosphoryl] [(3R)-2,2-dimethyl-3-oxidanyl-4-oxidanylidene-4-[[3-oxidanylidene-3-[2-(2-oxidanylideneheptadecylsulfanyl)ethylamino]propyl]amino]butyl] hydrogen phosphate / S-(2-オキソヘプタデシル)CoA
由来	homo sapiens (ヒト)
キーワード	TRANSFERASE (転移酵素) / membrane protein (膜タンパク質) / lipid synthesis (脂質代謝)