4HWY

Trypanosoma brucei procathepsin B solved from 40 fs free-electron laser pulse data by serial femtosecond X-ray crystallography

Summary for 4HWY

• Entry DOI: 10.2210/pdb4hwy/pdb
• Descriptor: Cysteine peptidase C (CPC), beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: papain fold, lysosomal cysteine protease, hydrolase
• Biological source: Trypanosoma brucei brucei TREU927 (Trypanosoma brucei brucei strain 927/4 GUTat10.1)
• Total number of polymer chains: 1
• Total formula weight: 38270.63

Authors

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.W.,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.,Shoemann, R.L.,Steinbrener, J.,Timneanu, N.,Wang, D.,Weierstall, U.,Zatsepin, N.A.,Spence, J.C.H.,Fromme, P.,Schlichting, I.,Duszenko, M.,Betzel, C.,Chapman, H. (deposition date: 2012-11-09, release date: 2012-12-05, Last modification date: 2024-10-09)

Primary citation

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.
Natively inhibited Trypanosoma brucei cathepsin B structure determined by using an X-ray laser.
Science, 339:227-230, 2013

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.

PubMed: 23196907
DOI: 10.1126/science.1229663

Experimental method

X-RAY DIFFRACTION (2.1 Å)