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51.
Steed PM Tansey MG Zalevsky J Zhukovsky EA Desjarlais JR Szymkowski DE Abbott C Carmichael D Chan C Cherry L Cheung P Chirino AJ Chung HH Doberstein SK Eivazi A Filikov AV Gao SX Hubert RS Hwang M Hyun L Kashi S Kim A Kim E Kung J Martinez SP Muchhal US Nguyen DH O'Brien C O'Keefe D Singer K Vafa O Vielmetter J Yoder SC Dahiyat BI 《Science (New York, N.Y.)》2003,301(5641):1895-1898
Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands. 相似文献
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Berry EW 《Science (New York, N.Y.)》1907,25(638):470-472
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Berry SS 《Science (New York, N.Y.)》1912,36(932):643-646
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Budanov AV Sablina AA Feinstein E Koonin EV Chumakov PM 《Science (New York, N.Y.)》2004,304(5670):596-600
Acting as a signal, hydrogen peroxide circumvents antioxidant defense by overoxidizing peroxiredoxins (Prxs), the enzymes that metabolize peroxides. We show that sestrins, a family of proteins whose expression is modulated by p53, are required for regeneration of Prxs containing Cys-SO(2)H, thus reestablishing the antioxidant firewall. Sestrins contain a predicted redox-active domain homologous to AhpD, the enzyme catalyzing the reduction of a bacterial Prx, AhpC. Purified Hi95 (sestrin 2) protein supports adenosine triphosphate-dependent reduction of overoxidized PrxI in vitro, indicating that unlike AhpD, which is a disulfide reductase, sestrins are cysteine sulfinyl reductases. As modulators of peroxide signaling and antioxidant defense, sestrins constitute potential therapeutic targets. 相似文献
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The absorption of ultra-violet light by three bacteriophages C13, C16 and C36, prepared with a strain of Escherichia communior has been determined. Each bacteriophage preparation showed a characteristic absorption curve, when the wave-length was plotted against the photographic density. Crude bacteriophage preparations absorbed more light than one such preparation obtained in a purer state, but the wavelength of maximum absorption remained the same. 相似文献
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Berry EW 《Science (New York, N.Y.)》1914,39(1001):357-358