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 language | English (US) |
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Pages (from-to) | 227-230 |
Number of pages | 4 |
Journal | Science |
Volume | 339 |
Issue number | 6116 |
DOIs | |
State | Published - Jan 11 2013 |
ASJC Scopus subject areas
- General
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Trypanosoma brucei procathepsin B solved from 40 fs free-electron laser pulse data by serial femtosecond X-ray crystallography
Redecke, L. (Contributor), Nass, K. (Contributor), DePonte, D. P. (Contributor), White, T. A. (Contributor), Rehders, D. (Contributor), Barty, A. (Contributor), Stellato, F. (Contributor), Liang, M. (Contributor), Barends, T. R. M. (Contributor), Boutet, S. (Contributor), Williams, G. J. (Contributor), Messerschmidt, M. (Contributor), Seibert, M. M. (Contributor), Aquila, A. (Contributor), Arnlund, D. (Contributor), Bajt, S. (Contributor), Barth, T. B. (Contributor), Bogan, M. J. (Contributor), Caleman, C. (Contributor), Chao, T. (Contributor), Doak, R. B. (Contributor), Fleckenstein, H. (Contributor), Frank, M. (Contributor), Fromme, R. (Contributor), Galli, L. (Contributor), Grotjohann, I. (Contributor), Hunter, M. S. (Contributor), Johansson, L. C. (Contributor), Kassemeyer, S. (Contributor), Katona, G. (Contributor), Kirian, R. (Contributor), Koopmann, R. (Contributor), Kupitz, C. (Contributor), Lomb, L. (Contributor), Martin, A. V. (Contributor), Mogk, S. (Contributor), Neutze, R. (Contributor), Shoeman, R. L. (Contributor), Steinbrener, J. (Contributor), Timneanu, N. (Contributor), Wang, D. (Contributor), Weierstall, U. (Contributor), Zatsepin, N. A. (Contributor), Spence, J. C. H. (Contributor), Fromme, P. (Contributor), Schlichting, I. (Contributor), Duszenko, M. (Contributor), Betzel, C. (Contributor) & Chapman, H. N. (Contributor), Protein Data Bank (PDB), Dec 5 2012
DOI: 10.2210/pdb4HWY, https://www.wwpdb.org/pdb?id=pdb_00004hwy
Dataset