Structural studies of bacterial pore-forming protein toxins

在这个项目中，将确定形成膜细胞壁孔隙的蛋白质的三维结构。这些蛋白质是细菌毒素，了解它们的结构可能有助于设计新的抗生素。该项目将重点研究一类被称为胆固醇依赖性细胞溶素的毒素，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，会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射线晶体学加以阐明。蛋白质晶体学是以接近原子的分辨率研究蛋白质的三维形状。用这种方法使蛋白质形成晶体。然后将x射线束照射到晶体上，使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完全了解其生物活性是必要的，对于合理设计可能改变其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.