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- SASDEB4: Tryparedoxin I109A, in the presence of inhibitor CFT (2-(chlorome... -
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Open data
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Basic information
Entry | Database: SASBDB / ID: SASDEB4 |
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![]() | Tryparedoxin I109A, in the presence of inhibitor CFT (2-(chloromethyl)-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one)
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Function / homology | ![]() thioredoxin-disulfide reductase (NADPH) activity / negative regulation of Wnt signaling pathway / negative regulation of protein ubiquitination / nucleus Similarity search - Function |
Biological species | ![]() ![]() |
![]() | ![]() Title: Inhibitor-Induced Dimerization of an Essential Oxidoreductase from African Trypanosomes. 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 ...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 / ![]() ![]() 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. |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
-Data source
SASBDB page | ![]() |
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-Related structure data
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External links
Related items in Molecule of the Month |
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-Models
Model #2350 | ![]() Type: atomic / Chi-square value: 1.23 / P-value: 0.000060 ![]() |
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Model #2351 | ![]() Type: atomic / Chi-square value: 1.23 / P-value: 0.000060 ![]() |
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Sample
![]() | Name: Tryparedoxin I109A, in the presence of inhibitor CFT (2-(chloromethyl)-5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one) |
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Buffer | Name: 10 mM HEPES pH 7.5, 50 mM NaCl / pH: 7.5 |
Entity #1275 | Type: protein / Description: Tryparedoxin I109A / Formula weight: 15.775 / Source: Trypanosoma brucei brucei / References: UniProt: O77404 Sequence: GSGLAKYLPG ATNLLSKSGE VSLGSLVGKT VFLYFSASWC PPCRGFTPVL AEFYEKHHVA KNFEVVLISW DENESDFHDY YGKMPWLALP FDQRSTVSEL GKTFGVESAP TLITINADTG AIIGTQARTR VIEDPDGANF PWPN |
-Experimental information
Beam | Instrument name: ESRF BM29 / City: Grenoble / 国: France ![]() | ||||||||||||||||||||||||||||||
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Detector | Name: Pilatus 1M / Type: Dectris / Pixsize x: 172 mm | ||||||||||||||||||||||||||||||
Scan |
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Distance distribution function P(R) |
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Result | Comments: SEC column type: GE Healthcare S75 3.2/300; Sample Injection Concentration = 10 mg/mL; Column flow-rate = 0.1 mL/min.
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