| Structural highlights
Publication Abstract from PubMed
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 obtain the room-temperature 2.1 A 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.
Natively Inhibited Trypanosoma brucei Cathepsin B Structure Determined by Using an X-ray Laser.,Redecke L, Nass K, Deponte DP, White TA, Rehders D, Barty A, Stellato F, Liang M, Barends TR, Boutet S, Williams GJ, Messerschmidt M, Seibert MM, Aquila A, Arnlund D, Bajt S, Barth T, Bogan MJ, Caleman C, Chao TC, Doak RB, Fleckenstein H, Frank M, Fromme R, Galli L, Grotjohann I, Hunter MS, Johansson LC, Kassemeyer S, Katona G, Kirian RA, Koopmann R, Kupitz C, Lomb L, Martin AV, Mogk S, Neutze R, Shoeman RL, Steinbrener J, Timneanu N, Wang D, Weierstall U, Zatsepin NA, Spence JC, Fromme P, Schlichting I, Duszenko M, Betzel C, Chapman HN Science. 2012 Nov 29. PMID:23196907[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Redecke L, Nass K, Deponte DP, White TA, Rehders D, Barty A, Stellato F, Liang M, Barends TR, Boutet S, Williams GJ, Messerschmidt M, Seibert MM, Aquila A, Arnlund D, Bajt S, Barth T, Bogan MJ, Caleman C, Chao TC, Doak RB, Fleckenstein H, Frank M, Fromme R, Galli L, Grotjohann I, Hunter MS, Johansson LC, Kassemeyer S, Katona G, Kirian RA, Koopmann R, Kupitz C, Lomb L, Martin AV, Mogk S, Neutze R, Shoeman RL, Steinbrener J, Timneanu N, Wang D, Weierstall U, Zatsepin NA, Spence JC, Fromme P, Schlichting I, Duszenko M, Betzel C, Chapman HN. Natively Inhibited Trypanosoma brucei Cathepsin B Structure Determined by Using an X-ray Laser. Science. 2012 Nov 29. PMID:23196907 doi:https://dx.doi.org/10.1126/science.1229663
|
