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データを開く
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基本情報
登録情報 | データベース: 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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機能・相同性 | ![]() thioredoxin-disulfide reductase (NADPH) activity / negative regulation of Wnt signaling pathway / negative regulation of protein ubiquitination / ![]() 類似検索 - 分子機能 |
生物種 | ![]() ![]() ![]() |
![]() | ![]() タイトル: Inhibitor-Induced Dimerization of an Essential Oxidoreductase from African Trypanosomes. 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 ...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 / ![]() ![]() 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. |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
-モデル
モデル #2350 | ![]() タイプ: atomic / カイ2乗値: 1.23 / P-value: 0.000060 ![]() |
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モデル #2351 | ![]() タイプ: atomic / カイ2乗値: 1.23 / P-value: 0.000060 ![]() |
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試料
![]() | 名称: 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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バッファ | 名称: 10 mM HEPES pH 7.5, 50 mM NaCl / pH: 7.5 |
要素 #1275 | タイプ: protein / 記述: Tryparedoxin I109A / 分子量: 15.775 / 由来: Trypanosoma brucei brucei / 参照: UniProt: O77404 配列: GSGLAKYLPG ATNLLSKSGE VSLGSLVGKT VFLYFSASWC PPCRGFTPVL AEFYEKHHVA KNFEVVLISW DENESDFHDY YGKMPWLALP FDQRSTVSEL GKTFGVESAP TLITINADTG AIIGTQARTR VIEDPDGANF PWPN |
-実験情報
ビーム | 設備名称: ESRF BM29 / 地域: Grenoble / 国: France ![]() ![]() | ||||||||||||||||||||||||||||||
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検出器 | 名称: Pilatus 1M / タイプ: Dectris / Pixsize x: 172 mm | ||||||||||||||||||||||||||||||
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距離分布関数 P(R) |
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結果 | コメント: 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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