Natively inhibited trypanosoma brucei cathepsin B structure determined by using an x-ray laser

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 B. Barth, Michael J. Bogan, Carl Caleman, Tzu Chiao ChaoR. 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, Henry N. Chapman

Research output: Contribution to journalArticle

304 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)227-230
Number of pages4
JournalScience
Volume339
Issue number6116
DOIs
Publication statusPublished - Jan 11 2013

    Fingerprint

ASJC Scopus subject areas

  • General

Cite this

Redecke, L., Nass, K., DePonte, D. P., White, T. A., Rehders, D., Barty, A., Stellato, F., Liang, M., Barends, T. R. M., Boutet, S., Williams, G. J., Messerschmidt, M., Seibert, M. M., Aquila, A., Arnlund, D., Bajt, S., Barth, T. B., Bogan, M. J., Caleman, C., ... Chapman, H. N. (2013). Natively inhibited trypanosoma brucei cathepsin B structure determined by using an x-ray laser. Science, 339(6116), 227-230. https://doi.org/10.1126/science.1229663