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	Inhibitor-Induced Dimerization of an Essential Oxidoreductase from African Trypanosomes.
ジャーナル・号・ページ	Angew Chem Int Ed Engl, Vol. 58, Issue 11, Page 3640-3644, Year 2019
掲載日	2019年3月11日
著者	Annika Wagner / Thien Anh Le / Martha Brennich / Philipp Klein / Nicole Bader / Erika Diehl / Daniel Paszek / A Katharina Weickhmann / Natalie Dirdjaja / R Luise Krauth-Siegel / Bernd Engels / Till Opatz / Hermann Schindelin / Ute A Hellmich /
PubMed 要旨	Trypanosomal and leishmanial infections claim tens of thousands of lives each year. The metabolism of these unicellular eukaryotic parasites differs from the human host and their enzymes thus ...Trypanosomal and leishmanial infections claim tens of thousands of lives each year. The metabolism of these unicellular eukaryotic parasites differs from the human host and their enzymes thus constitute promising drug targets. Tryparedoxin (Tpx) from Trypanosoma brucei is the essential oxidoreductase in the parasite's hydroperoxide-clearance cascade. In vitro and in vivo functional assays show that a small, selective inhibitor efficiently inhibits Tpx. With X-ray crystallography, SAXS, analytical SEC, SEC-MALS, MD simulations, ITC, and NMR spectroscopy, we show how covalent binding of this monofunctional inhibitor leads to Tpx dimerization. Intra- and intermolecular inhibitor-inhibitor, protein-protein, and inhibitor-protein interactions stabilize the dimer. The behavior of this efficient antitrypanosomal molecule thus constitutes an exquisite example of chemically induced dimerization with a small, monovalent ligand that can be exploited for future drug design.
リンク	Angew Chem Int Ed Engl / PubMed:30605929
手法	SAS (X-ray synchrotron) / X線回折
解像度	1.6 - 1.8 Å
構造データ	SASDE24: Tryparedoxin, in the presence of inhibitor CFT (2-(chloromethyl)-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one) 手法: SAXS/SANS SASDE34: Tryparedoxin W39A, reduced state (Tryparedoxin W39A) 手法: SAXS/SANS SASDE44: Tryparedoxin W39A, oxidized state (Tryparedoxin W39A) 手法: SAXS/SANS SASDE54: Tryparedoxin W39A, in the presence of inhibitor CFT (2-(chloromethyl)-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one) 手法: SAXS/SANS SASDE64: Tryparedoxin W70A, reduced state (Tryparedoxin W70A) 手法: SAXS/SANS SASDE74: Tryparedoxin W70A, oxidized state (Tryparedoxin W70A) 手法: SAXS/SANS SASDE84: Tryparedoxin W70A, in the presence of inhibitor CFT (2-(chloromethyl)-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one) 手法: SAXS/SANS SASDE94: Tryparedoxin I109A, reduced state (Tryparedoxin I109A) 手法: SAXS/SANS SASDEA4: Tryparedoxin I109A, oxidized state (Tryparedoxin I109A) 手法: SAXS/SANS SASDEB4: Tryparedoxin I109A, in the presence of inhibitor CFT (2-(chloromethyl)-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one) 手法: SAXS/SANS SASDEF4: Tryparedoxin K102E, reduced state (Tryparedoxin K102E) 手法: SAXS/SANS SASDEG4: Tryparedoxin K102E, oxidized state (Tryparedoxin K102E) 手法: SAXS/SANS SASDEH4: Tryparedoxin K102E, in the presence of inhibitor CFT (2-(chloromethyl)-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one) 手法: SAXS/SANS SASDEY3: Tryparedoxin, reduced state (Tryparedoxin) 手法: SAXS/SANS SASDEZ3: Tryparedoxin, oxidized state (Tryparedoxin) 手法: SAXS/SANS PDB-6gxg: Tryparedoxin from Trypanosoma brucei in complex with CFT 手法: X-RAY DIFFRACTION / 解像度: 1.6 Å PDB-6gxy: Tryparedoxin from Trypanosoma brucei in complex with CFT 手法: X-RAY DIFFRACTION / 解像度: 1.8 Å
化合物	ChemComp-FFN: 5-(4-fluorophenyl)-2-methyl-3~{H}-thieno[2,3-d]pyrimidin-4-one ChemComp-GOL: GLYCEROL / グリセロ-ル / グリセリン ChemComp-HOH: WATER / 水
由来	trypanosoma brucei brucei (ブルーストリパノソーマ)
キーワード	OXIDOREDUCTASE (酸化還元酵素) / Covalent Inhibitor / Photoreduction (光化学反応) / Inhibitor-Induced Dimerization / Monomer-Dimer Mixture