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241.
Crystal structure of the anthrax lethal factor. 总被引:13,自引:0,他引:13
A D Pannifer T Y Wong R Schwarzenbacher M Renatus C Petosa J Bienkowska D B Lacy R J Collier S Park S H Leppla P Hanna R C Liddington 《Nature》2001,414(6860):229-233
Lethal factor (LF) is a protein (relative molecular mass 90,000) that is critical in the pathogenesis of anthrax. It is a highly specific protease that cleaves members of the mitogen-activated protein kinase kinase (MAPKK) family near to their amino termini, leading to the inhibition of one or more signalling pathways. Here we describe the crystal structure of LF and its complex with the N terminus of MAPKK-2. LF comprises four domains: domain I binds the membrane-translocating component of anthrax toxin, the protective antigen (PA); domains II, III and IV together create a long deep groove that holds the 16-residue N-terminal tail of MAPKK-2 before cleavage. Domain II resembles the ADP-ribosylating toxin from Bacillus cereus, but the active site has been mutated and recruited to augment substrate recognition. Domain III is inserted into domain II, and seems to have arisen from a repeated duplication of a structural element of domain II. Domain IV is distantly related to the zinc metalloprotease family, and contains the catalytic centre; it also resembles domain I. The structure thus reveals a protein that has evolved through a process of gene duplication, mutation and fusion, into an enzyme with high and unusual specificity. 相似文献
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244.
Jinghui Li Rui Kang Ali Mosleh Xing Pan .School of Reliability Systems Engineering Beihang University Beijing P.R.China .Center for Risk Reliability University of Maryl College Park MD USA 《系统工程与电子技术(英文版)》2011,(6):1015-1022
This paper presents a methodology for automatically generating risk scenarios for dynamic reliability applications in which some dynamic characteristics(e.g.,the order,timing and magnitude of events,the value of relevant process parameters and initial conditions) have a significant influence on the evolution of the system.The main idea of the methodology is:(i) making the system model "express itself" through simulation by having the model driven by an elaborated simulation engine;(ii) exploiting uniform design to pick out a small subset of representative design points from the space of relevant dynamic characteristics;(iii) for each selected design point,employing a depth-first systematic exploration strategy to cover all possible scenario branches at each branch point.A highly dynamic example adapted from the literature(a chemical batch reactor) is studied to test the effectiveness of the proposed methodology. 相似文献
245.
We examined experimentally the flapping performance in terms of aerodynamic force generation of an insect-inspired flapper actuated by both of original LIPCA and compressed LIPCA. Flapping tests for two artificial wing shapes of horse botfly and hawk moth were conducted at the wing rotation angle of 60° and a flapping frequency range from 6 Hz to 12 Hz to find the optimum flapping frequency and to investigate the effect of compressed LIPCA and wing shape on the force generation. Flapping tests in the vacuum were also undertaken to measure the induced inertia force. The aerodynamic force was calculated by subtracting the inertia force from the total force measured in the air. It was found that the average inertia force was relatively small when compared with the average total force. The use of the compressed LIPCA could significantly improve the flapping angle of the flapper from 110° to 130° (18.2% increase) resulting in 24.5% increase in the average aerodynamic force. It was also found that flapper with hawk moth wings could produce larger force than the flapper with horse botfly wings. 相似文献
246.
研究管状曲面和它的平行曲面的奇点问题.所谓管状曲面,是沿着E3里一条曲线的双参数空间运动产生的.选定曲线的Frenet向量T作为旋转轴,用不同的方法得到了运动管状曲面的特征.然后,给出管状曲面奇点的一些定理和结果. 相似文献
247.
Most of the spare ordering policies treated up to now have assumed that preventive and corrective replacement costs are equal,
which implies in essential that there is no significant need for preventive replacement. This paper presents an ordering policy
for preventive age replacement with minimal repair. Introducing the replacement, repair, inventory holding and shortage costs,
the expected cost rate is derived. A procedure to determine jointly the ordering time for a spare and the preventive replacement
time for the operating unit so as to minimize the expected cost rate is proposed. To explain the ordering policy and the optimization
procedure, a numerical example is also included. 相似文献
248.
Woosuk Park 《Foundations of Science》2014,19(4):363-374
We can witness the recent surge of interest in the interaction between cognitive science, philosophy of science, and aesthetics on the problem of representation. This naturally leads us to rethinking the achievements of Goodman’s monumental book Languages of Art. For, there is no doubt that no one else contributed more than Goodman to throw a light on the cognitive function of art. Ironically, it could be also Goodman who has been the stumbling block for a unified theory of representation. In this paper, I shall contrast the ways how differently misrepresentation has been treated in cognitive science, aesthetics, and philosophy of science. And I shall show that it is Goodman’s unnecessary separation of resemblance and representation in art that made such a difference. As a conclusion, I will indicate some of the most promising projects toward the unified theory of representation the revolt against Goodman’s rejection of resemblance theories might promise to us. 相似文献
249.
Gurumurthy S Xie SZ Alagesan B Kim J Yusuf RZ Saez B Tzatsos A Ozsolak F Milos P Ferrari F Park PJ Shirihai OS Scadden DT Bardeesy N 《Nature》2010,468(7324):659-663
Haematopoietic stem cells (HSCs) can convert between growth states that have marked differences in bioenergetic needs. Although often quiescent in adults, these cells become proliferative upon physiological demand. Balancing HSC energetics in response to nutrient availability and growth state is poorly understood, yet essential for the dynamism of the haematopoietic system. Here we show that the Lkb1 tumour suppressor is critical for the maintenance of energy homeostasis in haematopoietic cells. Lkb1 inactivation in adult mice causes loss of HSC quiescence followed by rapid depletion of all haematopoietic subpopulations. Lkb1-deficient bone marrow cells exhibit mitochondrial defects, alterations in lipid and nucleotide metabolism, and depletion of cellular ATP. The haematopoietic effects are largely independent of Lkb1 regulation of AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling. Instead, these data define a central role for Lkb1 in restricting HSC entry into cell cycle and in broadly maintaining energy homeostasis in haematopoietic cells through a novel metabolic checkpoint. 相似文献
250.