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121.
Prabhash K. Pandey Dushyant Singh Farrukh Jamal 《Archives of insect biochemistry and physiology》2015,89(1):18-34
A trypsin inhibitor purified from the seeds of the Manila tamarind, Pithecellobium dulce (PDTI), was studied for its effects on growth parameters and developmental stages of Helicoverpa armigera. PDTI exhibited inhibitory activity against bovine trypsin (~86%; ~1.33 ug/ml IC50). The inhibitory activity of PDTI was unaltered over a wide range of temperature, pH, and in the presence of dithiothreitol. Larval midgut proteases were unable to digest PDTI for up to 12 h of incubation. Dixon and Lineweaver–Burk double reciprocal plots analysis revealed a competitive inhibition mechanism and a Ki of ~3.9 × 10?8 M. Lethal dose (0.50% w/w) and dosage for weight reduction by 50% (0.25% w/w) were determined. PDTI showed a dose‐dependent effect on mean larval weight and a series of nutritional disturbances. In artificial diet at 0.25% w/w PDTI, the efficiency of conversion of ingested food, of digested food, relative growth rate, and growth index declined, whereas approximate digestibility, relative consumption rate, metabolic cost, consumption index, and total developmental period were increased in larvae. This is the first report of antifeedant and antimetabolic activities of PDTI on midgut proteases of H. armigera. 相似文献
122.
Understanding factors that drive protein–protein association is of fundamental importance. We show that a single geometric parameter in crystal structures of protein–protein complexes, the angle between the electric dipole of one subunit and the partner‐generated electric field at the same subunit, linearly correlates with experimentally determined protein–protein association rates. Imprint of a dynamic kinetic process in a single static geometric parameter, associated with mutual electrostatic orientation of subunits in protein–protein complexes, is elegant and demonstrates the universality of electrostatic steering in attenuating protein–protein association rates. That the essence of a complex phenomenon could be captured by properties of the final crystal structure of the complex implies that the electrostatic orientations of protein subunits in crystal structures and the associated transition states are nearly identical. Further, the cosine of the angle, alone, is shown to be sufficient in predicting association rate constants, with accuracies comparable to currently available predictors that use more intricate methodologies. Our results offer mechanistic insights and could be useful in development of coarse‐grained models. Proteins 2015; 83:1557–1562. © 2015 Wiley Periodicals, Inc. 相似文献
123.
124.
Latitudinal gradients in the productivity of European migrant warblers have not shifted northwards during a period of climate change 下载免费PDF全文
125.
Effective virtual screening relies on our ability to make accurate prediction of protein-ligand binding, which remains a great challenge. In this work, utilizing the molecular-mechanics Poisson-Boltzmann (or Generalized Born) surface area approach, we have evaluated the binding affinity of a set of 156 ligands to seven families of proteins, trypsin β, thrombin α, cyclin-dependent kinase (CDK), cAMP-dependent kinase (PKA), urokinase-type plasminogen activator, β-glucosidase A, and coagulation factor Xa. The effect of protein dielectric constant in the implicit-solvent model on the binding free energy calculation is shown to be important. The statistical correlations between the binding energy calculated from the implicit-solvent approach and experimental free energy are in the range of 0.56-0.79 across all the families. This performance is better than that of typical docking programs especially given that the latter is directly trained using known binding data whereas the molecular mechanics is based on general physical parameters. Estimation of entropic contribution remains the barrier to accurate free energy calculation. We show that the traditional rigid rotor harmonic oscillator approximation is unable to improve the binding free energy prediction. Inclusion of conformational restriction seems to be promising but requires further investigation. On the other hand, our preliminary study suggests that implicit-solvent based alchemical perturbation, which offers explicit sampling of configuration entropy, can be a viable approach to significantly improve the prediction of binding free energy. Overall, the molecular mechanics approach has the potential for medium to high-throughput computational drug discovery. 相似文献
126.
Elucidating kinetic processes of protein–protein interactions (PPI) helps to understand how basic building blocks affect overall behavior of living systems. In this study, we used structure‐based properties to build predictive models for kinetic constants of PPI. A highly diverse PPI dataset, protein–protein kinetic interaction data and structures (PPKIDS), was built. PPKIDS contains 62 PPI with complex structures and kinetic constants measured experimentally. The influence of structural properties on kinetics of PPI was studied using 35 structure‐based features, describing different aspects of complex structures. Linear models for the prediction of kinetic constants were built by fitting with selected subsets of structure‐based features. The models gave correlation coefficients of 0.801, 0.732, and 0.770 for koff, kon, and Kd, respectively, in leave‐one‐out cross validations. The predictive models reported here use only protein complex structures as input and can be generally applied in PPI studies as well as systems biology modeling. Our study confirmed that different properties play different roles in the kinetic process of PPI. For example, kon was affected by overall structural features of complexes, such as the composition of secondary structures, the change of translational and rotational entropy, and the electrostatic interaction; while koff was determined by interfacial properties, such as number of contacted atom pairs per 100 Å2. This information provides useful hints for PPI design. Proteins 2010;79:720–734. © 2010 Wiley‐Liss, Inc. 相似文献
127.
Park JY Jeong HJ Kim YM Park SJ Rho MC Park KH Ryu YB Lee WS 《Bioorganic & medicinal chemistry letters》2011,21(18):5602-5604
As part of our ongoing effort to develop influenza virus neuraminidase (NA) inhibitors from various medicinal plants, we utilized bioassay-guided fractionation to isolated six alkylated chalcones (1-6) from Angelica keiskei. Xanthokeistal A (1) emerged as new compound containing the rare alkyl substitution, 6,6-dimethoxy-3-methylhex-2-enyl. When we tested the ability of these individual alkyl substituted chalcones to inhibit influenza virus NA hydrolysis, we found that 2-hydroxy-3-methyl-3-butenyl alkyl (HMB) substituted chalcone (3, IC(50)=12.3 μM) showed most potent inhibitory activity. The order of potency of substituted alkyl groups on for NA inhibition was HMB>6-hydroxyl-3,7-dimethyl-octa-2,7-dienyl>dimethylallyl>geranyl. All NA inhibitors screened were found to be reversible noncompetitive inhibitors. 相似文献
128.
Yamauchi K Sai G 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2011,153(3):328-335
We investigated the interaction of 2,4,6-triiodophenol (TIP), a potent thyroid hormone disrupting chemical, with serum proteins from rainbow trout (Onchorhynchus mykiss), bullfrog (Rana catesbeiana), chicken (Gallus gallus), pig (Sus scrofa domesticus), and rat (Rattus norvegicus) using a [(125)I]TIP binding assay, gel filtration chromatography, and native polyacrylamide gel electrophoresis. [(125)I]TIP bound non-specifically to proteins in trout serum, specifically but weakly to proteins in bullfrog serum, and specifically and strongly to proteins in chicken, pig, and rat serum samples. Candidate TIP-binding proteins included lipoproteins (220-320kDa) in trout, albumin in bullfrog, albumin and transthyretin (TTR) in chicken and pig, and TTR in rat. TTR in the chicken, pig, and rat serum samples was responsible for the high-affinity, low-capacity binding sites for TIP (dissociation constant 2.2-3.5×10(-10)M). In contrast, a weak interaction of [(125)I]TIP with tadpole serum proteins accelerated [(125)I]TIP cellular uptake in vitro. Intraperitoneal injection of [(125)I]TIP in tadpoles revealed that the radioactivity was predominantly accumulated in the gallbladder and the kidney. The differences in the molecular and binding properties of TIP binding proteins among vertebrates would affect in part the cellular availability, tissue distribution and clearance of TIP. 相似文献
129.
Piazza F Rios Pde L Fanelli D Bongini L Skoglund U 《European biophysics journal : EBJ》2005,34(7):899-911
The encounter between anisotropic agents in diffusion-controlled reactions is a topic of very general relevance in chemistry and biology. Here we introduce a simplified model of encounter of an isotropic molecule with a pair of partially reacting agents and apply it to the encounter reaction between an antibody and its antigen. We reduce the problem to the solution of dual series relations, which can be solved iteratively, yielding the exact solution for the encounter rate constant at any desired order of accuracy. We quantify the encounter effectiveness by means of a simple indicator and show that the two binding centers systematically behave in an anti-cooperative fashion. However, we demonstrate that a reduction of the binding active sites allows the composite molecule to recover binding effectiveness, in spite of the overall reduction of the rate constant. In addition, we provide a simple formula that enables one to calculate the anti-cooperativity as a function of the size of the binding site for any values of the separation between the two active lobes and of the antigen size. Finally, some biological implications of our results are discussed. 相似文献
130.
A. M. Timofeev T. V. Borovkova N. M. Nydenova T. V. Akhlynina D. A. Shmarov N. I. Grineva 《Molecular Biology》2005,39(2):210-217
A study was conducted of the interaction of an octadecameric oligodeoxynucleotide (dON) containing the BCL2 mRNA translation start with K562 cells. Both in solution and upon lipofection, the binding of dON used at a low concentration (30 nM) at 37°C involved two steps: saturating surface binding with the cell membrane and internalization. Three phases were revealed in the dynamics of internalization: the extent and rate of internalization increased during the first hour of incubation; decreased during the second hour; and then increased again, which was assumed to reflect the priming of new dON-binding sites. The binding constant and the number of binding sites were estimated at 10°C (the conditions preventing internalization) by consecutive dissociation of dON-cell complexes formed in 1 h at 37°C. Incubation of dON with cells led to the priming of new high-affinity binding sites and an increase of the binding constant to a level characteristic of high-affinity ligand-receptor interactions (109 M–1). High-affinity receptor-mediated binding preceded internalization of dON. Lipofection increased the binding constant and the number of binding sites severalfold but had virtually no effect on the temporal pattern and the extent of dON internalization.__________Translated from Molekulyarnaya Biologiya, Vol. 39, No. 2, 2005, pp. 235–244.Original Russian Text Copyright © 2005 by Timofeev, Borovkova, Nydenova, Akhlynina, Shmarov, Grineva. 相似文献