4pb1

Publication Abstract from PubMed

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 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.

Structural basis of nucleoside and nucleoside drug selectivity by concentrative nucleoside transporters.,Johnson ZL, Lee JH, Lee K, Lee M, Kwon DY, Hong J, Lee SY Elife. 2014 Jul 31:e03604. doi: 10.7554/eLife.03604. PMID:25082345^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.