Transport systems are responsible for the uptake of essential nutrients and ions, excretion of end products of metabolism, efflux of toxic substances and communication between cells and the environment. Fast growing genome-sequencing data and a wealth of biochemical, molecular and genetic literature has revealed thousands of members of transporter superfamilies. Most of the transporters share some common features, e.g. multiple alpha-helical transmembrane domains. However, they function differently in terms of mechanism and substrate specificity, and other characteristics. Analysis of sequence similarities suggests they may have different evolutionary origins and belong to unrelated families. In this research we use oligopeptide transporters as examples to investigate some of the structure-function relationships. The oligopeptide transport systems play an important role in the transporting of pharmacologically active peptide-like drugs in addition to the absorption and reclamation of natural small peptides. Understanding how oligopeptide transporters work is of great interest to both biological research and clinical application. Due to the difficulty to determine the 3-D structures of membrane proteins, we are using bioinformatics approaches in this research. The first goal of this project is to identify peptide transporters through database searching and analysis using available tools as well as those self-developed. At the end of the project, we expect to set up a criteria to assign each member to a specific subgroup. Another important goal is to investigate the literature to retrieve published information related to each of the transporters, e.g. substrate specificity and affinity, energy coupling mechanism, related disease pattern, function and regulation, etc. This information is essential to infer structure-function relationships of transporters. Finally, based on the research and information retrieved, the third goal of this project is to generate a prototype database for drug transporters that contains some of these relationships.
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