Many Ways to Derivatize Macromolecules and Their Crystals for Phasing.
Many Ways to Derivatize Macromolecules and Their Crystals for Phasing.
复制标题
DOI：
10.1007/978-1-4939-7000-1_14
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Dauter Z
中科院分区：
文献类型：
--
作者：
Dauter M;Dauter Z
由于蛋白质数据库中有许多大分子模型，目前大多数晶体结构都是通过分子置换来解决的。然而，真正新颖的结构只能通过特殊原子方法的一个版本来解决。特殊原子如硫、磷或金属可以天然存在于大分子中，或者可以在衍生化过程中有意引入。然后利用这些特殊原子对X射线的同晶和/或异常散射进行定相。有许多方法可以获得潜在有用的衍生物，从通过基因工程或化学合成将特殊原子引入蛋白质或核酸，到将天然晶体浸泡在具有重原子和/或有害散射原子的适当化合物的溶液中。没有任何方法能保证最终成功，衍生化在很大程度上仍然是一个试错过程。然而，在实践中，有一个很好的机会，各种各样的可用程序之一将导致成功的结构解决方案。
Due to the availability of many macromolecular models in the Protein Data Bank, the majority of crystal structures are currently solved by molecular replacement. However, truly novel structures can only be solved by one of the versions of the special-atom method. The special atoms such as sulfur, phosphorus or metals could be naturally present in the macromolecules, or could be intentionally introduced in a derivatization process. The isomorphous and/or anomalous scattering of X-rays by these special atoms is then utilized for phasing. There are many ways to obtain potentially useful derivatives, ranging from the introduction of special atoms to proteins or nucleic acids by genetic engineering or by chemical synthesis, to soaking native crystals in solutions of appropriate compounds with heavy and/or anomalously scattering atoms. No approach guarantees the ultimate success and derivatization remains largely a trial-and-error process. In practice, however, there is a very good chance that one of a wide variety of the available procedures will lead to successful structure solution.