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991.
Glycogen synthase kinase 3beta (GSK 3beta) is a key component of several cellular processes including Wnt and insulin signalling pathways. The interaction of GSK3beta with scaffolding peptide axin is thought to be responsible for the effective phosphorylation of beta-catenin, the core effector of Wnt signaling, which has been linked with the occurrence of colon cancer and melanoma. It has been demonstrated that the binding of axin to GSK3beta is abolished by the single-point mutation of Val267 to Gly (V267G) in GSK3beta or Leu392 to Pro (L392P) in axin. Molecular dynamics (MD) simulations were performed on wild type (WT), V267G mutant and L392P one to elucidate the two unbinding mechanisms that occur through different pathways. Besides, rough energy and residue-based energy decomposition were calculated by MM_GBSA (molecular mechanical Generalized_Born surface area) approach to illuminate the instability of the two mutants. The MD simulations of the two mutants and WT reveal that the structure of GSK3beta remains unchanged, while axin moves away from the interfacial hydrophobic pockets in both two mutants. Axin exhibits positional shift in V267G mutant, whereas, losing the hydrogen bonds that are indispensable for stabilizing the helix structure of wild type axin, the helix of axin is distorted in L392P mutant. To conclude, both two mutants destroy the hydrophobic interaction that is essential to the stability of GSK3beta-axin complex. 相似文献
992.
Certain sequences, known as chameleon sequences, take both alpha- and beta-conformations in natural proteins. We demonstrate that a wild chameleon sequence fused to the C-terminal alpha-helix or beta-sheet in foreign stable proteins from hyperthermophiles forms the same conformation as the host secondary structure. However, no secondary structural formation is observed when the sequence is attached to the outside of the secondary structure. These results indicate that this sequence inherently possesses an ability to make either alpha- or beta-conformation, depending on the sequentially neighboring secondary structure if little other nonlocal interaction occurs. Thus, chameleon sequences take on a satellite state through contagion by the power of a secondary structure. We propose this "conformational contagion" as a new nonlocal determinant factor in protein structure and misfolding related to protein conformational diseases. 相似文献
993.
Hubs in the protein-protein interaction network have been classified as "party" hubs, which are highly correlated in their mRNA expression with their partners while "date" hubs show lesser correlation. In this study, we explored the role of intrinsic disorder in date and party hub interactions. The data reveals that intrinsic disorder is significantly enriched in date hub proteins when compared with party hub proteins. Intrinsic disorder has been largely implicated in transient binding interactions. The disorder to order transition, which occurs during binding interactions in disordered regions, renders the interaction highly reversible while maintaining the high specificity. The enrichment of intrinsic disorder in date hubs may facilitate transient interactions, which might be required for date hubs to interact with different partners at different times. 相似文献
994.
Through bioinformatics and experimental approaches, we have assigned the first biochemical property to a predicted protein product in the human genome as a new 14-3-3 binding protein. 14-3-3 client proteins represent a diverse group of regulatory molecules that often function as signaling integrators in response to various environmental cues and include proteins such as Bad and Foxo. Using 14-3-3 as a probe in a yeast two-hybrid screen, we identified a novel 14-3-3 binding protein with unknown function, initially designated as clone 546. Confocal microscopy revealed that clone 546 localized to the nucleus of mammalian cells. Additional studies show that the gene encoding clone 546 is expressed in many human tissues, including the thymus, as well as a number of cancer cell lines. The interaction of clone 546 with 14-3-3 was confirmed in mammalian cells. Interestingly, this interaction was markedly enhanced by the expression of activated Akt/PKB, suggesting a phosphorylation dependent event. Mutational analysis was carried out to identify Ser479 as the predominant residue that mediates the clone 546/14-3-3 association. Phosphorylation of Ser479 by AKT/PKB further supports a critical role for Akt/PKB in regulation of the clone 546/14-3-3 interaction. On the basis of these findings, we named this undefined protein FAKTS: Fourteen-three-three associated AKT Substrate. 相似文献
995.
Although plant quality can indirectly increase the performance of the third trophic level by bottom-up cascading effects,
the mechanisms of this indirect effect are still unclear. In this study the carbon–nitrogen stoichiometry in a tri-trophic
system consisting of the willow, a leaf beetle, and a predatory ladybird beetle were examined to determine the mechanisms
of the bottom-up cascading effect. The bottom-up cascade is initiated by increasing leaf nitrogen, because of artificial cutting
of willow trees. The relative growth rate (RGR) of the leaf beetle increased when fed on cut willow leaves, because of the
high leaf nitrogen in the cut willows. Ladybird beetle RGR also increased when fed on leaf beetles fed on cut willow leaves.
The increased RGR of the ladybirds cannot be explained by the quality of the prey, however, because leaf beetle nitrogen was
not affected by host plant quality. Thus, the carbon–nitrogen stoichiometry could not be a mechanism of the bottom-up cascade
through multiple trophic levels. 相似文献
996.
Shaoyao-Gancao-Tang (SGT), a traditional Chinese herbal medicine (Kampo formulation) containing Shaoyao (Paeoniae Radix) and Gancao (Glycyrrhizae Radix), is co-administered with laxative sodium picosulfate as a premedication for relieving the pain accompanying colonoscopy. Paeoniflorin (PF), an active glycoside of SGT, is metabolized into the antispasmodic agent paeonimetabolin-I (PM-I) by intestinal bacteria after oral administration. The objective of the present study was to investigate whether the co-administered laxative (sodium picosulfate) influences the metabolism of PF to PM-I by intestinal bacteria. We found that the PF-metabolizing activity of intestinal bacteria in rat feces was significantly reduced to approximately 34% of initial levels by a single sodium picosulfate pretreatment and took approximately 6 days to recover. Repeated administration of SGT after the sodium picosulfate pretreatment significantly shortened the recovery period to around 2 days. Similar results were also observed for plasma PM-I concentration. Since PM-I has muscle relaxant activity, the present results suggest that repetitive administration of SGT after sodium picosulfate pretreatment might be useful to relieve the pain associated with colonoscopy. 相似文献
997.
Preferences for grouping with familiar individuals are shown in many animal species, including the three-spined stickleback (Gasterosteus aculeatus). Shoaling with familiars is advantageous because of more precise anti-predator behaviours or more stable dominance hierarchies. Additionally, associations with familiar individuals facilitate the evolution of altruistic behaviour. Thus, in situations of increased competition one might expect an increased preference for familiar fish. We gave single juvenile sticklebacks of different nutritional state the choice between shoals composed either of familiar or unfamiliar individuals. Satiated fish preferred to shoal with familiar individuals. A comparative analysis of 8 stickleback studies with 15 different tests using familiars showed that all tests gave similar results, i.e. sticklebacks of all age classes preferred to shoal with familiars in a non-sexual context. In contrast, hungry test fish did not prefer to shoal with familiar fish, but even showed a preference for the unfamiliar group. Because sticklebacks use early-life familiarity to recognize kin, the results suggest the avoidance of competition with relatives. To our knowledge, this is the first study showing an impact of nutritional state on social interactions with familiar individuals. 相似文献
998.
The thermodynamics of biological interactions is frequently studied by the van't Hoff analysis whereby data on variation of the binding constant K(D) with temperature are used to obtain estimates of standard enthalpy (Delta H degrees ), entropy (Delta S degrees ), and heat capacity (Delta C degrees P) of complex formation. A Monte Carlo simulation demonstrates that the absolute error of the above parameters is proportional to the relative error of KD and independent of the actual values of KD and of the way they vary with temperature. The error of Delta H degrees is approximately the same as that of T Delta S degrees (within 14% in the temperature range 5-45 degrees C). The error depends both on the number of temperature points within the experimental temperature range and on the size of the range, but it is more sensitive to the latter. Using the linear form of the van't Hoff equation to fit data with non-zero Delta C degrees P gives erroneous Delta H degrees and DeltaS degrees estimates at standard temperature except for the case when the T points are placed symmetrically with respect to the standard temperature. With the range of Delta C degrees P values usual for protein-protein interactions, the KD error must be very low to confidently infer that Delta C degrees P is non-zero or to claim that two interactions have different Delta C degrees P. 相似文献
999.
1000.
Mandrika I Prusis P Yahorava S Tars K Wikberg JE 《Journal of molecular recognition : JMR》2007,20(2):97-102
The aim of this study was to develop predictive quantitative structure-activity relationship (QSAR) modeling for antibody-peptide interactions. A small single chain antibody library was designed and manufactured around the murine anti-p24 (HIV-1) monoclonal antibody CB4-1 by use of statistical molecular design (SMD) principles and site directed mutagenesis, and its affinity for a p24 derived antigen was determined by fluorescence polarization. A satisfactory QSAR model (Q(2) = 0.74, R(2) = 0.88) was derived by correlating the affinity data to physicochemical property scales of the amino acids varied in the library. The model explains most of the antibody-antigen interactions of the studied set, and provides insights into the molecular mechanism involved in antigen binding. 相似文献