| Literature DB >> 23196907 |
Lars Redecke1,2, Karol Nass3,4, Daniel P DePonte3, Thomas A White3, Dirk Rehders1, Anton Barty3, Francesco Stellato3, Mengning Liang3, Thomas R M Barends5,6, Sébastien Boutet7, Garth J Williams7, Marc Messerschmidt7, M Marvin Seibert7, Andrew Aquila3, David Arnlund8, Sasa Bajt9, Torsten Barth10, Michael J Bogan11, Carl Caleman3, Tzu-Chiao Chao12, R Bruce Doak13, Holger Fleckenstein3, Matthias Frank14, Raimund Fromme12, Lorenzo Galli3,4, Ingo Grotjohann12, Mark S Hunter12, Linda C Johansson8, Stephan Kassemeyer5,6, Gergely Katona8, Richard A Kirian3,13, Rudolf Koopmann10, Chris Kupitz12, Lukas Lomb5,6, Andrew V Martin3, Stefan Mogk10, Richard Neutze8, Robert L Shoeman5,6, Jan Steinbrener5,6, Nicusor Timneanu15, Dingjie Wang13, Uwe Weierstall13, Nadia A Zatsepin13, John C H Spence13, Petra Fromme12, Ilme Schlichting5,6, Michael Duszenko10, Christian Betzel16, Henry N Chapman3,4.
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.Entities:
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Year: 2012 PMID： 23196907 PMCID： PMC3786669 DOI： 10.1126/science.1229663
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728