Structural basis of nucleoside and nucleoside drug selectivity by concentrative nucleoside transporters.

Journal Article (Journal Article)

Concentrative nucleoside transporters (CNTs) are responsible for cellular entry of nucleosides, which serve as precursors to nucleic acids and act as signaling molecules. CNTs also play a crucial role in the uptake of nucleoside-derived drugs, including anticancer and antiviral agents. Understanding how CNTs recognize and import their substrates could not only lead to a better understanding of nucleoside-related biological processes but also the design of nucleoside-derived drugs that can better reach their targets. Here, we present a combination of X-ray crystallographic and equilibrium-binding studies probing the molecular origins of nucleoside and nucleoside drug selectivity of a CNT from Vibrio cholerae. We then used this information in chemically modifying an anticancer drug so that it is better transported by and selective for a single human CNT subtype. This work provides proof of principle for utilizing transporter structural and functional information for the design of compounds that enter cells more efficiently and selectively.

Full Text

Duke Authors

Cited Authors

  • Johnson, ZL; Lee, J-H; Lee, K; Lee, M; Kwon, D-Y; Hong, J; Lee, S-Y

Published Date

  • July 31, 2014

Published In

Volume / Issue

  • 3 /

Start / End Page

  • e03604 -

PubMed ID

  • 25082345

Pubmed Central ID

  • PMC4139061

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.03604


  • eng

Conference Location

  • England