研究人员发现防癌化合物

日本神户大学研究生院教授片冈徹领导的研究小组说，他们发现了能遏制Ras蛋白质功能的化合物，这种蛋白质的生成如果由于基因突变而出现异常，就可能引发某些癌症。



该小组在新一期美国《国家科学院学报》网络版上报告说，编码合成Ras蛋白质的基因如果突变，Ras蛋白质就会与其他蛋白质结合，传递使细胞癌变的信号，是一种重要的致癌因素。研究小组指出，约20%的癌症是由于这个原因所致，其在大肠癌和胰腺癌的致病原因中所占比例尤其高。

研究小组曾利用大型同步辐射光源“SPring-8”对Ras蛋白质进行分析，发现其表面存在能与化合物结合的袋状结构。研究小组认为，如果找到与这种袋状结构结合的特定化合物，就可以阻碍Ras蛋白质与其他蛋白质结合，从而阻碍癌变信号的传递，防止癌变。

研究小组通过计算机模拟演算和实验，从约4万种候选物质中选出3种，将其命名为“神户家族化合物”。在向移植了人类大肠癌细胞的实验鼠投放这种化合物后，研究人员发现，与投放之前相比，癌组织的大小缩减至原有尺寸的约50%。

这3种化合物都是有机化合物，容易生产，所以研究小组认为用它们制造药物并不困难。

原文链接：

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Structure of Sr-substituted photosystem II at 2.1 Å resolution and its implications in the mechanism of water oxidation


Oxygen-evolving complex of photosystem II (PSII) is a tetra-manganese calcium penta-oxygenic cluster (Mn4CaO5) catalyzing light-induced water oxidation through several intermediate states (S-states) by a mechanism that is not fully understood. To elucidate the roles of Ca2+ in this cluster and the possible location of water substrates in this process, we crystallized Sr2+-substituted PSII from Thermosynechococcus vulcanus, analyzed its crystal structure at a resolution of 2.1 Å, and compared it with the 1.9 Å structure of native PSII. Our analysis showed that the position of Sr was moved toward the outside of the cubane structure of the Mn4CaO5-cluster relative to that of Ca2+, resulting in a general elongation of the bond distances between Sr and its surrounding atoms compared with the corresponding distances in the Ca-containing cluster. In particular, we identified an apparent elongation in the bond distance between Sr and one of the two terminal water ligands of Ca2+, W3, whereas that of the Sr-W4 distance was not much changed. This result may contribute to the decrease of oxygen evolution upon Sr2+-substitution, and suggests a weak binding and rather mobile nature of this particular water molecule (W3), which in turn implies the possible involvement of this water molecule as a substrate in the O-O bond formation. In addition, the PsbY subunit, which was absent in the 1.9 Å structure of native PSII, was found in the Sr-PSII structure。

来源：科学网