In the never ending battle between infectious organisms and modern medicine there is a constant need for novel approaches to fight pathogenic invasions due to the rapid rate in which pathogens develop new means to resist drug treatment. A number of therapeutic approaches rely on targeting structural differences between the infectious organism and their host.
We aim to exploit differences in the ubiquitous use of sugars between pathogen and host in effort to derive novel therapeutic targets to fight infections. In both prokaryotic and eukaryotic organisms, sugars are used for the generation of energy and as structural components. As sugars are attached to other molecules forming glycoproteins and glycolipids, they have distinct roles in cell recognition and adhesion. This proposal focuses on the structural and functional characterization of two glycosylation-related transporter families?the sialic acid and the nucleotide sugar transporter families?that are expressed in a number of pathogenic bacteria and protozoan and fungal parasites, but are not present in humans and therefore represent therapeutic targets to fight pathogenic infections. Specifically, we aim to resolve x-ray crystal structures and biochemically characterize members of the sialic acid and nucleotide sugar transporter families. Currently, there is no structural information for either class of transporter available. All the ingredients for a groundbreaking period of research are in place, as we will capitalize on our protein expression, purification, and crystallization platforms and our extensive experience working with other classes of membrane transport proteins. In fact, we already have obtained well-diffracting crystals and established functional assays for both transporters.
Each aim on its own is capable of producing exciting results, but together they will provide a complete picture of transport by two structurally uncharacterized classes of transporters.
In the never ending battle between infectious organisms and modern medicine there is a constant need for novel approaches to fight pathogenic invasion. This proposal focuses on the structural and functional characterization of two glycosylation-related secondary active transporter families that are expressed in a number of pathogenic bacteria and protozoan and fungal parasites but are not present in humans and therefore represent therapeutic targets to fight pathogenic infections.
