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	X-ray and cryo-EM structures of inhibitor-bound cytochrome complexes for structure-based drug discovery.
ジャーナル・号・ページ	IUCrJ, Vol. 5, Issue Pt 2, Page 200-210, Year 2018
掲載日	2018年3月1日
著者	Kangsa Amporndanai / Rachel M Johnson / Paul M O'Neill / Colin W G Fishwick / Alexander H Jamson / Shaun Rawson / Stephen P Muench / S Samar Hasnain / Svetlana V Antonyuk /
PubMed 要旨	Cytochrome , a dimeric multi-subunit electron-transport protein embedded in the inner mitochondrial membrane, is a major drug target for the treatment and prevention of malaria and toxoplasmosis. ...Cytochrome , a dimeric multi-subunit electron-transport protein embedded in the inner mitochondrial membrane, is a major drug target for the treatment and prevention of malaria and toxoplasmosis. Structural studies of cytochrome from mammalian homologues co-crystallized with lead compounds have underpinned structure-based drug design to develop compounds with higher potency and selectivity. However, owing to the limited amount of cytochrome that may be available from parasites, all efforts have been focused on homologous cytochrome complexes from mammalian species, which has resulted in the failure of some drug candidates owing to toxicity in the host. Crystallographic studies of the native parasite proteins are not feasible owing to limited availability of the proteins. Here, it is demonstrated that cytochrome is highly amenable to single-particle cryo-EM (which uses significantly less protein) by solving the apo and two inhibitor-bound structures to ∼4.1 Å resolution, revealing clear inhibitor density at the binding site. Therefore, cryo-EM is proposed as a viable alternative method for structure-based drug discovery using both host and parasite enzymes.
リンク	IUCrJ / PubMed:29765610 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	3.1 - 4.4 Å
構造データ	4286 6fo0 EMDB-4286, PDB-6fo0: CryoEM structure of bovine cytochrome bc1 in complex with the anti-malarial compound GSK932121 手法: EM (単粒子) / 解像度: 4.1 Å 4288 6fo2 EMDB-4288, PDB-6fo2: CryoEM structure of bovine cytochrome bc1 with no ligand bound 手法: EM (単粒子) / 解像度: 4.4 Å 4292 6fo6 EMDB-4292, PDB-6fo6: CryoEM structure of bovine cytochrome bc1 in complex with the anti-malarial inhibitor SCR0911 手法: EM (単粒子) / 解像度: 4.1 Å PDB-5okd: Crystal structure of bovine Cytochrome bc1 in complex with inhibitor SCR0911. 手法: X-RAY DIFFRACTION / 解像度: 3.1 Å
化合物	ChemComp-PG4: TETRAETHYLENE GLYCOL / テトラエチレングリコ-ル / 沈殿剤YM / ポリエチレングリコール ChemComp-6PE: 1,2-DIHEXANOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE / [O-(1-O,2-O-ジヘキサノイル-L-グリセロ-3-ホスホ)-2-アミノエタノ-ル]アニオン ChemComp-CDL: CARDIOLIPIN / リン脂質YM / Cardiolipin ChemComp-HEM: PROTOPORPHYRIN IX CONTAINING FE / Heme B ChemComp-9XE: 7-methoxy-3-methyl-2-[5-[4-(trifluoromethyloxy)phenyl]pyridin-3-yl]-1~{H}-quinolin-4-one ChemComp-LMT: DODECYL-BETA-D-MALTOSIDE / ドデシルβ-D-マルトシド / 可溶化剤YM ChemComp-PEE: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine / DOPE, リン脂質YM / Discrete optimized protein energy ChemComp-HEC: HEME C / Heme C ChemComp-PO4: PHOSPHATE ION / ホスファ-ト / リン酸塩 ChemComp-FES: FE2/S2 (INORGANIC) CLUSTER / 鉄・硫黄クラスター ChemComp-PX4: 1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / ジミリストイルホスファチジルコリン / DMPC, リン脂質YM / Dimyristoylphosphatidylcholine ChemComp-HOH: WATER / 水 ChemComp-G8U: 3-chloro-6-(hydroxymethyl)-2-methyl-5-{4-[3-(trifluoromethoxy)phenoxy]phenyl}pyridin-4-ol ChemComp-DY2*: 7-methoxy-3-methyl-2-[5-[4-(trifluoromethyloxy)phenyl]pyridin-3-yl]quinolin-4-ol
由来	bos taurus (ウシ) Bovine (ウシ)
キーワード	ELECTRON TRANSPORT (電子伝達系) / antimalarial inhibitor / Qi site binder / MEMBRANE PROTEIN (膜タンパク質) / Cryo-EM (低温電子顕微鏡法) / Inhibitor binding (酵素阻害剤) / cytochrome bc1 (ユビキノール-シトクロムcレダクターゼ)