Structural studies of bacterial pore-forming protein toxins

在这个项目中，将确定在膜细胞壁中形成孔的蛋白质的三维结构。这些蛋白质是细菌毒素，对其结构的了解可能会对设计新的抗生素有用。该项目将专注于一种名为胆固醇依赖型细胞溶血素的毒素，这种毒素由革兰氏阳性细菌(如梭状芽胞杆菌和链球菌)释放，可导致各种严重的传染病，如气性坏疽、肺炎和脑膜炎。三维结构将用X射线结晶学来阐明。蛋白质结晶学是研究蛋白质在近原子分辨率下的三维形状的学科。在这种方法中，蛋白质被制成晶体。然后，X射线束照射到晶体上，导致X射线以蛋白质三维形状的特征模式散射。了解蛋白质的结构对于全面了解它们的生物活性是必要的，对于合理设计可能改变它们活性的新药也是非常有用的。

In this project the three-dimensional structures of proteins that form pores in membrane cell walls will be determined. These proteins are bacterial toxins and knowledge of their structure may prove useful in the design of new antibiotics. This project will focus on a class of toxins called the cholesterol-dependent cytolysins which are released by Gram positive bacteria such as Clostridia and Streptococcus and which cause a variety of nasty infectious diseases such as gas gangrene, pneumonia and meningitis. The three-dimensional structures will be elucidated using X-ray crystallography. Protein crystallography is the study of three-dimensional shapes of proteins at near atomic resolution. In this method proteins are made to form crystals. X-ray beams are then shone on the crystals causing the X-rays to scatter in a pattern which is characteristic of the protein's three-dimensional shape. Knowledge of the structure of proteins is necessary for the complete understanding of their biological activity and is also very useful for the rational design of new drugs that may alter their activity.