Natively inhibited Trypanosoma brucei cathepsin B structure determined by using an X-ray laser.
Natively inhibited Trypanosoma brucei cathepsin B structure determined by using an X-ray laser.
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DOI：
10.1126/science.1229663
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发表时间：
2013-01-11
期刊：
影响因子：
--
通讯作者：
Chapman HN
中科院分区：
文献类型：
--
作者：
Redecke L;Nass K;DePonte DP;White TA;Rehders D;Barty A;Stellato F;Liang M;Barends TRM;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 JCH;Fromme P;Schlichting I;Duszenko M;Betzel C;Chapman HN
布氏锥虫半胱氨酸蛋白酶组织蛋白酶B（TbCatB）参与宿主蛋白质降解，是开发针对昏睡病的新疗法的有希望的靶点，昏睡病是由这种原生动物寄生虫引起的致命疾病。TbCatB的成熟、活性形式的结构迄今为止还没有为设计针对T的安全和特异性药物提供足够的信息。布鲁塞。通过结合两个最近的创新，在体内结晶和串行飞秒晶体学，我们得到了室温2.1埃分辨率的TbCatB的完全糖基化的前体复合物的结构。该结构揭示了天然TbCatB抑制的机制，并表明可以通过X射线自由电子激光的“破坏前衍射”方法从数十万个个体微晶中获得新的生物分子信息。
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.
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影响因子：
48
作者：
Koopmann, Rudolf;Cupelli, Karolina;Redecke, Lars;Nass, Karol;DePonte, Daniel P.;White, Thomas A.;Stellato, Francesco;Rehders, Dirk;Liang, Mengning;Andreasson, Jakob;Aquila, Andrew;Bajt, Sasa;Barthelmess, Miriam;Barty, Anton;Bogan, Michael J.;Bostedt, Christoph;Boutet, Sebastien;Bozek, John D.;Caleman, Carl;Coppola, Nicola;Davidsson, Jan;Doak, R. Bruce;Ekeberg, Tomas;Epp, Sascha W.;Erk, Benjamin;Fleckenstein, Holger;Foucar, Lutz;Graafsma, Heinz;Gumprecht, Lars;Hajdu, Janos;Hampton, Christina Y.;Hartmann, Andreas;Hartmann, Robert;Hauser, Guenter;Hirsemann, Helmut;Holl, Peter;Hunter, Mark S.;Kassemeyer, Stephan;Kirian, Richard A.;Lomb, Lukas;Maia, Filipe R. N. C.;Kimmel, Nils;Martin, Andrew V.;Messerschmidt, Marc;Reich, Christian;Rolles, Daniel;Rudek, Benedikt;Rudenko, Artem;Schlichting, Ilme;Schulz, Joachim;Seibert, M. Marvin;Shoeman, Robert L.;Sierra, Raymond G.;Soltau, Heike;Stern, Stephan;Strueder, Lothar;Timneanu, Nicusor;Ullrich, Joachim;Wang, Xiaoyu;Weidenspointner, Georg;Weierstall, Uwe;Williams, Garth J.;Wunderer, Cornelia B.;Fromme, Petra;Spence, John C. H.;Stehle, Thilo;Chapman, Henry N.;Betzel, Christian;Duszenko, Michael
通讯作者：
Duszenko, Michael
DOI：
10.1126/science.1217737
发表时间：
2012-07-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Boutet S;Lomb L;Williams GJ;Barends TR;Aquila A;Doak RB;Weierstall U;DePonte DP;Steinbrener J;Shoeman RL;Messerschmidt M;Barty A;White TA;Kassemeyer S;Kirian RA;Seibert MM;Montanez PA;Kenney C;Herbst R;Hart P;Pines J;Haller G;Gruner SM;Philipp HT;Tate MW;Hromalik M;Koerner LJ;van Bakel N;Morse J;Ghonsalves W;Arnlund D;Bogan MJ;Caleman C;Fromme R;Hampton CY;Hunter MS;Johansson LC;Katona G;Kupitz C;Liang M;Martin AV;Nass K;Redecke L;Stellato F;Timneanu N;Wang D;Zatsepin NA;Schafer D;Defever J;Neutze R;Fromme P;Spence JC;Chapman HN;Schlichting I
通讯作者：
Schlichting I
影响因子：
4.8
作者：
Illy, C;Quraishi, O;Mort, JS
通讯作者：
Mort, JS
DOI：
10.1007/s00018-004-4445-9
发表时间：
2005-03
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Dubin G
通讯作者：
Dubin G
影响因子：
3.8
作者：
Abdulla, Maha-Hamadien;O'Brien, Theresa;McKerrow, James H.
通讯作者：
McKerrow, James H.