science20130111-9

来自德国的科学家利用目前最新的两项技术——活体结晶技术和串行飞秒激光结晶技术,在室温下获得昏睡病致病寄生虫——布氏锥虫(Trypanosoma brucei)半胱氨酸蛋白酶组织蛋白酶B(TbCatB)的晶体结构(分辨率为2.1埃)。这项发现将有助于科学家们找到与这种前肽结构相似的分子,开发出杀死这种寄生虫的安全特异性药物。

-2013年1月11日《科学》

中文翻译


【题目】利用X射线激光技术获得布氏锥虫天然钝化的组织蛋白酶B的结构

【译文】布氏锥虫(Trypanosoma brucei)半胱氨酸蛋白酶组织蛋白酶B(TbCatB)是一种参与宿主蛋白降解的酶,它是一个有价值的干预靶标,可用于昏睡病新治疗策略的开发,昏睡病是一类由布氏锥虫引起的致死性疾病。迄今为止,科学家还未从成熟的、具有活性的TbCatB的结构上获得足够的信息来设计出杀死布氏锥虫的安全特异性药物。结合利用目前最新的两项技术——活体结晶技术和串行飞秒激光结晶技术,本研究在室温下获得完全糖基化的TbCatB前体复合物的晶体结构(分辨率为2.1埃)。该晶体结构揭示了天然TbCatB的钝化机制,同时表明利用X射线无电子激光技术的“破坏前衍射”方法,可从成千上万的生物微晶中获得新的结构信息。

英文原稿


[Title]: Natively Inhibited Trypanosoma brucei Cathepsin B Structure Determined by Using an X-ray Laser 

[Authors]: Lars Redecke, Karol Nass, Daniel P. DePonte, Thomas A. White, Dirk Rehders, Anton Barty, Francesco Stellato, Mengning Liang, Thomas R.M. Barends, Sébastien Boutet, Garth J. Williams, Marc Messerschmidt, M. Marvin Seibert, Andrew Aquila, David Arnlund, Sasa Bajt, Torsten Barth, Michael J. Bogan, Carl Caleman, Tzu-Chiao Chao, R. Bruce Doak, Holger Fleckenstein, Matthias Frank, Raimund Fromme, Lorenzo Galli, Ingo Grotjohann, Mark S. Hunter, Linda C. Johansson, Stephan Kassemeyer, Gergely Katona, Richard A. Kirian, Rudolf Koopmann, Chris Kupitz, Lukas Lomb, Andrew V. Martin, Stefan Mogk, Richard Neutze, Robert L. Shoeman, Jan Steinbrener, Nicusor Timneanu, Dingjie Wang, Uwe Weierstall, Nadia A. Zatsepin, John C. H. Spence, Petra Fromme, Ilme Schlichting, Michael Duszenko, Christian Betzel, and Henry N. Chapman

[Abstract]: The Trypanosoma brucei cysteine protease cathepsin B (TbCatB), which is involved in host protein degradation, is a promising target to develop new treatments against sleeping sickness, a fatal disease caused by this protozoan parasite. The structure of the mature, active form of TbCatB has so far not provided sufficient information for the design of a safe and specific drug against T. brucei. By combining two recent innovations, in vivo crystallization and serial femtosecond crystallography, we obtained the room-temperature 2.1 angstrom resolution structure of the fully glycosylated precursor complex of TbCatB. The structure reveals the mechanism of native TbCatB inhibition and demonstrates that new biomolecular information can be obtained by the “diffraction-before-destruction” approach of x-ray free-electron lasers from hundreds of thousands of individual microcrystals.

原文地址

http://www.sciencemag.org/content/339/6116/227.abstract

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