Structural and kinetic studies into eukaryotic sialyltransferases

The outer surfaces of mammalian cells are covered with a dense and complex array of sugar molecules. These sugars are important in many essential biological processes such as cell recognition, communication, neuron growth and immune defence. However, they are also used as attachment sites by a diverse range of disease-causing microbes and their toxins, and have been implicated in tumour cell metastasis. Many of these sugar-containing structures contain an essential sugar, sialic acid. The enzymes that transfer sialic acid onto these sugar structures are known as sialyltransferases. These enzymes are able to recognize numerous different types of sugar configurations. In fact, the human genome encodes at least 20 distinct sialyltransferases. Despite the importance of these enzymes, researchers know little about their molecular structure, their mechanisms, how they recognize their targets or how they are regulated. Dr. Francesco Rao is investigating the structure and mechanism of a mammalian sialyltransferase. This will give, for the first time, insight into how such enzymes work at the molecular level. This information could also be used to determine ways these enzymes could be therapeutically inhibited to combat infection or cancer metastasis.