University of Oulu
Supervisor: Veli-Pekka Jaakola
The SLC29 family of protein consists of four members of equilibrative nucleoside transporters (ENTs). ENTs are recently characterized and poorly understood group of membrane proteins that are important in uptake of endogenous nucleoside essential for nucleic acids and nucleotides synthesis. These proteins are also responsible for the cellular uptake of nucleoside analogue use to treat cancer, HIV and many other viral diseases. All four isoforms are widely distributed in mammalian tissue, although their relative abundance varies. Human equilibtrative nucleoside transporter 1 (hENT1) and hENT2 are the best characterized members of the family, however, little is known about their structure-function relationship. On the other hand, hENT3 and hENT4 are the recently identified nucleoside transporters, however, pharmacological studies on these transporters yet have not been taken in details. The main purpose of this research is the functional and structural characterization of hENTs. This research would be helpful in our understanding of molecular mechanism of nucleoside transport to explore the pharmaceutical potentials of these vital proteins. In a longer perspective, functional and structure studies with nucleoside analogues and ENTs inhibitors would assist us in designing novel anticancer and antiviral drugs.
Keywords: nucleoside transporters, function-structure-relationship, x-ray crystallography, EPR/NMR/fluorescence spectroscopy, conformational analysis