Download MendeleyNatively inhibited Trypanosoma brucei cathepsin B structure determined by using an X-ray laser.
Redecke, L., Nass, K., DePonte, D.P., White, T.A., Rehders, D., Barty, A., Stellato, F., Liang, M., Barends, T.R., Boutet, S., Williams, G.J., Messerschmidt, M., Seibert, M.M., Aquila, A., Arnlund, D., Bajt, S., Barth, T., Bogan, M.J., Caleman, C., Chao, T.C., Doak, R.B., Fleckenstein, H., Frank, M., Fromme, R., Galli, L., Grotjohann, I., Hunter, M.S., Johansson, L.C., Kassemeyer, S., Katona, G., Kirian, R.A., Koopmann, R., Kupitz, C., Lomb, L., Martin, A.V., Mogk, S., Neutze, R., Shoeman, R.L., Steinbrener, J., Timneanu, N., Wang, D., Weierstall, U., Zatsepin, N.A., Spence, J.C., Fromme, P., Schlichting, I., Duszenko, M., Betzel, C., Chapman, H.N.(2013) Science 339: 227-230
- PubMed: 23196907
- DOI: https://doi.org/10.1126/science.1229663
- Primary Citation of Related Structures:
4HWY - PubMed 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.
Organizational Affiliation:
Joint Laboratory for Structural Biology of Infection and Inflammation, Institute of Biochemistry and Molecular Biology, University of Hamburg, and Institute of Biochemistry, University of Lübeck, at Deutsches Elektronen-Synchrotron (DESY), Notkestrasse 85, 22607 Hamburg, Germany.
