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111.
Liu F Park JE Qian WJ Lim D Scharow A Berg T Yaffe MB Lee KS Burke TR 《ACS chemical biology》2012,7(5):805-810
In an effort to develop improved binding antagonists of the polo-like kinase 1 (Plk1) polo-box domain (PBD), we optimized interactions of the known high affinity 5-mer peptide PLHSpT using oxime-based post solid-phase peptide diversification of the N-terminal Pro residue. This allowed us to achieve up to two orders of magnitude potency enhancement. An X-ray crystal structure of the highest affinity analogue in complex with Plk1 PBD revealed new binding interactions in a hydrophobic channel that had been occluded in X-ray structures of the unliganded protein. This study represents an important example where amino acid modification by post solid-phase oxime ligation can facilitate the development of protein-protein interaction inhibitors by identifying new binding pockets that would not otherwise be accessible to coded amino acid residues. 相似文献
112.
Andrej Pavlovi? 《Plant signaling & behavior》2012,7(2):295-297
Carnivorous pitcher plants of the genus Nepenthes have evolved a great diversity of pitcher morphologies. Selective pressures for maximizing nutrient uptake have driven speciation and diversification of the genus in a process known as adaptive radiation. This leads to the evolution of pitchers adapted to specific and often bizarre source of nutrients, which are not strictly animal-derived. One example is Nepenthes ampullaria with unusual growth pattern and pitcher morphology what enables the plant to capture a leaf litter from the canopy above. We showed that the plant benefits from nitrogen uptake by increased rate of photosynthesis and growth what may provide competitive advantage over others co-habiting plants. A possible impact of such specialization toward hybridization, an important mechanism in speciation, is discussed. 相似文献
113.
Henderson R Sali A Baker ML Carragher B Devkota B Downing KH Egelman EH Feng Z Frank J Grigorieff N Jiang W Ludtke SJ Medalia O Penczek PA Rosenthal PB Rossmann MG Schmid MF Schröder GF Steven AC Stokes DL Westbrook JD Wriggers W Yang H Young J Berman HM Chiu W Kleywegt GJ Lawson CL 《Structure (London, England : 1993)》2012,20(2):205-214
This Meeting Review describes the proceedings and conclusions from the inaugural meeting of the Electron Microscopy Validation Task Force organized by the Unified Data Resource for 3DEM (http://www.emdatabank.org) and held at Rutgers University in New Brunswick, NJ on September 28 and 29, 2010. At the workshop, a group of scientists involved in collecting electron microscopy data, using the data to determine three-dimensional electron microscopy (3DEM) density maps, and building molecular models into the maps explored how to assess maps, models, and other data that are deposited into the Electron Microscopy Data Bank and Protein Data Bank public data archives. The specific recommendations resulting from the workshop aim to increase the impact of 3DEM in biology and medicine. 相似文献
114.
Brvar M Perdih A Hodnik V Renko M Anderluh G Jerala R Solmajer T 《Bioorganic & medicinal chemistry》2012,20(8):2572-2580
Bacterial DNA gyrase is an established and validated target for the development of novel antibacterials. In our previous work, we identified a novel series of bacterial gyrase inhibitors from the class of 4-(2,4-dihydroxyphenyl) thiazoles. Our ongoing effort was designated to search for synthetically more available compounds with possibility of hit to lead development. By using the virtual screening approach, new potential inhibitors were carefully selected from the focused chemical library and tested for biological activity. Herein we report on a novel class of 5-(2-hydroxybenzylidene) rhodanines as gyrase B inhibitors with activity in low micromolar range and moderate antibacterial activity. The binding of the two most active compounds to the enzyme target was further characterised using surface plasmon resonance (SPR) and differential scanning fluorimetry methods (DSF). 相似文献
115.
Cokl A 《Journal of insect physiology》2008,54(7):1113-1124
In solitary plant-dwelling stink bug species, success depends crucially on efficient mate location and recognition, mediated by signals transmitted through the plant. All stink bugs investigated so far communicate with species and sex-specific narrow-band calling and courtship song signals produced by abdomen vibration. Calling songs of lower specificity are characterized by readily repeated units emitted with regular repetition rate from the same place on a plant, while courtship songs take place at shorter distances in the process of species and sex recognition, together with signals of other modalities. Signal spectra with about 100Hz fundamental frequency and harmonics below 1000Hz are tuned to the resonant properties of their green host plants. The majority of the identified leg vibratory receptor cells and the underlying ventral cord interneurons respond best in the frequency range below 500Hz. Green plants with low pass filtering properties transmit optimally signals with a dominant frequency around 100Hz and strongly attenuate vibrations above 600Hz. Accurate tuning of signal spectral properties with the plant's mechanical characteristics enables communication over several meter distances, with dispersive bending waves running through the plant's rod-like structures under standing wave conditions. 相似文献
116.
Cong Y Topf M Sali A Matsudaira P Dougherty M Chiu W Schmid MF 《Journal of molecular biology》2008,375(2):331-336
Actin carries out many of its cellular functions through its filamentous form; thus, understanding the detailed structure of actin filaments is an essential step in achieving a mechanistic understanding of actin function. The acrosomal bundle in the Limulus sperm has been shown to be a quasi-crystalline array with an asymmetric unit composed of a filament with 14 actin-scruin pairs. The bundle in its true discharge state penetrates the jelly coat of the egg. Our previous electron crystallographic reconstruction demonstrated that the actin filament cross-linked by scruin in this acrosomal bundle state deviates significantly from a perfect F-actin helix. In that study, the tertiary structure of each of the 14 actin protomers in the asymmetric unit of the bundle filament was assumed to be constant. In the current study, an actin filament atomic model in the acrosomal bundle has been refined by combining rigid-body docking with multiple actin crystal structures from the Protein Data Bank and constrained energy minimization. Our observation demonstrates that actin protomers adopt different tertiary conformations when they form an actin filament in the bundle. The scruin and bundle packing forces appear to influence the tertiary and quaternary conformations of actin in the filament of this biologically active bundle. 相似文献
117.
Förster F Webb B Krukenberg KA Tsuruta H Agard DA Sali A 《Journal of molecular biology》2008,382(4):1089-1106
A major challenge in structural biology is to determine the configuration of domains and proteins in multidomain proteins and assemblies, respectively. All available data should be considered to maximize the accuracy and precision of these models. Small-angle X-ray scattering (SAXS) efficiently provides low-resolution experimental data about the shapes of proteins and their assemblies. Thus, we integrated SAXS profiles into our software for modeling proteins and their assemblies by satisfaction of spatial restraints. Specifically, we modeled the quaternary structures of multidomain proteins with structurally defined rigid domains as well as quaternary structures of binary complexes of structurally defined rigid proteins. In addition to SAXS profiles and the component structures, we used stereochemical restraints and an atomic distance-dependent statistical potential. The scoring function is optimized by a biased Monte Carlo protocol, including quasi-Newton and simulated annealing schemes. The final prediction corresponds to the best scoring solution in the largest cluster of many independently calculated solutions. To quantify how well the quaternary structures are determined based on their SAXS profiles, we used a benchmark of 12 simulated examples as well as an experimental SAXS profile of the homotetramer d-xylose isomerase. Optimization of the SAXS-dependent scoring function generally results in accurate models if sufficiently precise approximations for the constituent rigid bodies are available; otherwise, the best scoring models can have significant errors. Thus, SAXS profiles can play a useful role in the structural characterization of proteins and assemblies if they are combined with additional data and used judiciously. Our integration of a SAXS profile into modeling by satisfaction of spatial restraints will facilitate further integration of different kinds of data for structure determination of proteins and their assemblies. 相似文献
118.
Teaching high school students about the digestive system can be a challenge for a teacher when s/he wants to overcome rote learning of facts without a deeper understanding of the physiological processes inside the alimentary tract. A series of model experiments illustrating the journey of a sandwich was introduced into teaching high school biology. Using a computer equipped with a commercially available data-acquisition system and a couple of sensors, it was possible to illustrate the basic underlying physical and chemical principles of digestion to the students. Students were able to investigate, through hands-on activities, the chewing force of the jaws, importance of the mechanical breakdown of food, enzymatic activity of pepsin and amylase, antibacterial activity of hydrochloric acid, and importance of the villi for absorption. Students found the experiments interesting and helpful for understanding the digestive process. Furthermore, the results from testing indicated that the students had a deeper understanding of the physiological processes. 相似文献
119.
The effect of vibratory disturbance on sexual behaviour and substrate-borne sound communication of the southern green stink
bug, Nezara viridula L. was studied. Disturbance signals do not change the time N. viridula males need to locate the source of vibratory signals, but decrease the number of males responding with the calling and courtship
song to calling females. Female N. viridula proceed calling during stimulation with disturbance signals but some of them change the song rhythm by skipping one or more
signal intervals or emitting the repelling signals. The number of females which change the dominant frequency of the calling
song decreases proportionally with increasing differences between the dominant frequency of the disturbance signals and the
emitted female calling song. Variation of the song dominant frequency probably serves females to avoid interference by increasing
the signal to noise ratio. Signal duration and repetition rate do not change significantly when the female is stimulated with
the disturbance signals. This indicates that frequency shift by calling females is the main strategy for reducing interference
by competitive signalers in N. viridula vibrational communication. 相似文献
120.
Junqueira M Spirin V Balbuena TS Thomas H Adzhubei I Sunyaev S Shevchenko A 《Journal of Proteomics》2008,71(3):346-356
Homology-driven proteomics is a major tool to characterize proteomes of organisms with unsequenced genomes. This paper addresses practical aspects of automated homology-driven protein identifications by LC-MS/MS on a hybrid LTQ Orbitrap mass spectrometer. All essential software elements supporting the presented pipeline are either hosted at the publicly accessible web server, or are available for free download. 相似文献