排序方式: 共有23条查询结果,搜索用时 0 毫秒
11.
12.
13.
Friedrich R Panizzi P Fuentes-Prior P Richter K Verhamme I Anderson PJ Kawabata S Huber R Bode W Bock PE 《Nature》2003,425(6957):535-539
Many bacterial pathogens secrete proteins that activate host trypsinogen-like enzyme precursors, most notably the proenzymes of the blood coagulation and fibrinolysis systems. Staphylococcus aureus, an important human pathogen implicated in sepsis and endocarditis, secretes the cofactor staphylocoagulase, which activates prothrombin, without the usual proteolytic cleavages, to directly initiate blood clotting. Here we present the 2.2 A crystal structures of human alpha-thrombin and prethrombin-2 bound to a fully active staphylocoagulase variant. The cofactor consists of two domains, each with three-helix bundles; this is a novel fold that is distinct from known serine proteinase activators, particularly the streptococcal plasminogen activator streptokinase. The staphylocoagulase fold is conserved in other bacterial plasma-protein-binding factors and extracellular-matrix-binding factors. Kinetic studies confirm the importance of isoleucine 1 and valine 2 at the amino terminus of staphylocoagulase for zymogen activation. In addition to making contacts with the 148 loop and (pro)exosite I of prethrombin-2, staphylocoagulase inserts its N-terminal peptide into the activation pocket of bound prethrombin-2, allosterically inducing functional catalytic machinery. These investigations demonstrate unambiguously the validity of the zymogen-activation mechanism known as 'molecular sexuality'. 相似文献
14.
15.
North TE Goessling W Walkley CR Lengerke C Kopani KR Lord AM Weber GJ Bowman TV Jang IH Grosser T Fitzgerald GA Daley GQ Orkin SH Zon LI 《Nature》2007,447(7147):1007-1011
16.
Jürgen Schnekenburger Ina-Alexandra Weber Daniela Hahn Igor Buchwalow Burkhard Krüger Elke Albrecht Wolfram Domschke Markus M. Lerch 《Cellular and molecular life sciences : CMLS》2009,66(15):2525-2537
The regulated secretion of pancreatic zymogens depends on a functional cytoskeleton and intracellular vesicle transport. To
study the dynamics of tubulin and its motor proteins dynein and kinesin during secretion in pancreatic acinar cells, we infused
rats with 0.1 μg/kg/h caerulein. Electron and fluorescence microscopy detected neither dynein nor kinesin at the apical secretory
pole, nor on the surface of mature zymogen granules. After 30 min of secretagogue stimulation, kinesin and the Golgi marker
protein 58 K were reallocated towards the apical plasma membrane and association of kinesin with tubulin was enhanced. Disruption
of acinar cell microtubules had no effect on initial caerulein-induced amylase release but completely blocked secretion during
a second stimulus. Our results suggest that mature zymogen granule exocytosis is independent of intact microtubules, kinesin
and dynein. However, microtubule-dependent mechanisms seem to be important for the replenishment of secretory vesicles by
redistribution of Golgi elements towards the apical cell pole.
J. Schnekenburger and I.-A. Weber have contributed equally to this work. 相似文献
17.
X-ray crystallography and nuclear magnetic resonance measurements provide us with atomically resolved structures of an ever-growing number of biomolecules. These static structural snapshots are important to our understanding of biomolecular function, but real biomolecules are dynamic entities that often exploit conformational changes and transient molecular interactions to perform their tasks. Nuclear magnetic resonance methods can follow such structural changes, but only on millisecond timescales under non-equilibrium conditions. Time-resolved X-ray crystallography has recently been used to monitor the photodissociation of CO from myoglobin on a subnanosecond timescale, yet remains challenging to apply more widely. In contrast, two-dimensional infrared spectroscopy, which maps vibrational coupling between molecular groups and hence their relative positions and orientations, is now routinely used to study equilibrium processes on picosecond timescales. Here we show that the extension of this method into the non-equilibrium regime allows us to observe in real time in a short peptide the weakening of an intramolecular hydrogen bond and concomitant opening of a beta-turn. We find that the rate of this process is two orders of magnitude faster than the 'folding speed limit' established for contact formation between protein side chains. 相似文献
18.
19.
20.
Muhammad Azeem Munawar Dirk Wolfram Schubert Shahzad Maqsood Khan Muhammad Atiq Ur Rehman Nafisa Gull Atif Islam Aneela Sabir Muhammad Shafiq Bilal Haider Mudassar Azam Saba Urooge Khan Monika M. Voigt 《自然科学进展(英文版)》2018,28(3):266-274
This paper presents a study on the Design of Experiments(Do E) approach to optimize the fabrication parameters of titania(TiO_2) embedded glass fiber reinforced polyester hybrid composites(HCs). HCs of unsaturated polyester resin(UPR) were fabricated using methyl ethyl ketone peroxide(MEKP) as the curing agent by hand lay-up process(HLUP) and compression molding technique(CMT). The fabrication parameters were optimized by Taguchi Do E(an orthogonal array of L25) using 3 control factors(concentration of TiO_2, concentration of MEKP and curing temperature) having 5 levels each. Statistical tools were employed to identify significant factors affecting tensile strengths and its reproducibility during HLUP. It was found that the concentration of TiO_2 in HCs significantly influenced the tensile strength(TS) followed by MEKP concentration and curing temperature. The highest value of TS was obtained at 3 wt% TiO_2, 2 wt% MEKP and 80 °C. Nevertheless, the sensitivity of TiO_2 concentration was basis for fabrication of polyester titania glass fiber hybrids(PTGFHs), which were further investigated for density and void fractions, linear shrinkage, flexural strength, impact strength, hardness and thermal behaviors. Moreover, cross-linking and hydrogen-bonding between polymeric chains, styrene, silica content of glass fiber and TiO_2 particles in PTGFHs were confirmed by Fourier transform infrared spectroscopy. 相似文献