基于网络药理学的谷糠结合态多酚抗乳腺癌机制研究

本研究旨在探讨谷糠结合态多酚(bound phenol of inner shell,BPIS)发挥抗乳腺癌细胞活性的作用机制。首先采用细胞计数法检测BPIS对乳腺癌细胞以及正常乳腺细胞活性的影响;然后综合运用SEA、SIB以及GeneCards等数据库获得BPIS和乳腺癌的相关靶点,并分析活性成分与作用靶点的互作网络以及通路。本研究筛选得到BPIS抗乳腺癌相关靶点39个,主要涉及糖脂代谢和细胞自噬等生物过程以及MAPK、PI3K/AKT、FoxO等多条信号通,表明BPIS抗乳腺癌是多成分、多靶点、多通路协同作用的过程,而与细胞死亡相关的细胞自噬很可能在BPIS抑制乳腺癌过程中发挥主要作用。     

Solution structure and dynamics of the central CCP module pair of a poxvirus complement control protein

The complement control protein (CCP) module (also known as SCR, CCP or sushi domain) is prevalent amongst proteins that regulate complement activation. Functional and mutagenesis studies have shown that in most cases two or more neighbouring CCP modules form specific binding sites for other molecules. Hence the orientation in space of a CCP module with respect to its neighbours and the flexibility of the intermodular junction are likely to be critical for function. Vaccinia virus complement control protein (VCP) is a complement regulatory protein composed of four tandemly arranged CCP modules. The solution structure of the carboxy-terminal half of this protein (CCP modules 3 and 4) has been solved previously. The structure of the central portion (modules 2 and 3, VCP approximately 2,3) has now also been solved using NMR spectroscopy at 37 degrees C. In addition, the backbone dynamics of VCP approximately 2,3 have been characterised by analysis of its (15)N relaxation parameters. Module 2 has a typical CCP module structure while module 3 in the context of VCP approximately 2,3 has some modest but significant differences in structure and dynamics to module 3 within the 3,4 pair. Modules 2 and 3 do not share an extensive interface, unlike modules 3 and 4. Only two possible NOEs were identified between the bodies of the modules, but a total of 40 NOEs between the short intermodular linker of VCP approximately 2,3 and the bodies of the two modules determines a preferred, elongated, orientation of the two modules in the calculated structures. The anisotropy of rotational diffusion has been characterised from (15)N relaxation data, and this indicates that the time-averaged structure is more compact than suggested by (1)H-(1)H NOEs. The data are consistent with the presence of many intermodular orientations, some of which are kinked, undergoing interconversion on a 10(-8)-10(-6) second time-scale. A reconstructed representation of modules 2-4 allows visualisation of the spatial arrangement of the 11 substitutions that occur in the more potent complement inhibitor from Variola (small pox) virus.     

The bottom line for prediction of residue solvent accessibility

A simple method of predicting residue solvent accessibilities in proteins is described, with the intention that it should be used as a baseline by which more sophisticated approaches to prediction can be judged. Comparison with existing methods of predicting residue burial reveals that their performance is often little better than that of the baseline method. The problem of comparing different prediction methods is shown to be complicated by the proliferation of different schemes for classifying residue burial.