Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Inhibitor-induced dimerization of an essential oxidoreductase from African Trypanosomes.
Journal, issue, pages	Angew. Chem. Int. Ed. Engl., Year 2019 Jan 3
Publish date	May 31, 2018 (data collection date)
Authors	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 Abstract	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.
External links	Angew. Chem. Int. Ed. Engl. / PubMed:30605929
Methods	SAS (X-ray synchrotron) / X-ray diffraction
Resolution	1.6 - 1.8 Å
Structure data	SASDE24: Tryparedoxin, in the presence of inhibitor CFT (2-(chloromethyl)-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one) Method: SAXS/SANS SASDE34: Tryparedoxin W39A, reduced state (Tryparedoxin W39A) Method: SAXS/SANS SASDE44: Tryparedoxin W39A, oxidized state (Tryparedoxin W39A) Method: SAXS/SANS SASDE54: Tryparedoxin W39A, in the presence of inhibitor CFT (2-(chloromethyl)-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one) Method: SAXS/SANS SASDE64: Tryparedoxin W70A, reduced state (Tryparedoxin W70A) Method: SAXS/SANS SASDE74: Tryparedoxin W70A, oxidized state (Tryparedoxin W70A) Method: SAXS/SANS SASDE84: Tryparedoxin W70A, in the presence of inhibitor CFT (2-(chloromethyl)-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one) Method: SAXS/SANS SASDE94: Tryparedoxin I109A, reduced state (Tryparedoxin I109A) Method: SAXS/SANS SASDEA4: Tryparedoxin I109A, oxidized state (Tryparedoxin I109A) Method: SAXS/SANS SASDEB4: Tryparedoxin I109A, in the presence of inhibitor CFT (2-(chloromethyl)-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one) Method: SAXS/SANS SASDEF4: Tryparedoxin K102E, reduced state (Tryparedoxin K102E) Method: SAXS/SANS SASDEG4: Tryparedoxin K102E, oxidized state (Tryparedoxin K102E) Method: SAXS/SANS SASDEH4: Tryparedoxin K102E, in the presence of inhibitor CFT (2-(chloromethyl)-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one) Method: SAXS/SANS SASDEY3: Tryparedoxin, reduced state (Tryparedoxin) Method: SAXS/SANS SASDEZ3: Tryparedoxin, oxidized state (Tryparedoxin) Method: SAXS/SANS PDB-6gxg: Tryparedoxin from Trypanosoma brucei in complex with CFT Method: X-RAY DIFFRACTION / Resolution: 1.6 Å PDB-6gxy: Tryparedoxin from Trypanosoma brucei in complex with CFT Method: X-RAY DIFFRACTION / Resolution: 1.8 Å
Chemicals	ChemComp-FFN: 5-(4-fluorophenyl)-2-methyl-3~{H}-thieno[2,3-d]pyrimidin-4-one ChemComp-GOL: GLYCEROL / Glycerol ChemComp-HOH: WATER / Water
Source	trypanosoma brucei brucei (eukaryote)
Keywords	OXIDOREDUCTASE / Covalent Inhibitor / Photoreduction / Inhibitor-Induced Dimerization / Monomer-Dimer Mixture