4PD5

Crystal structure of vcCNT-7C8C bound to gemcitabine

Summary for 4PD5

• Entry DOI: 10.2210/pdb4pd5/pdb
• Related: 3TIJ 4PB1 4PB2 4PD7 4PD8 4PD9 4PDA
• Descriptor: NupC family protein, GEMCITABINE, SODIUM ION, ... (5 entities in total)
• Functional Keywords: membrane protein, sodium-coupled transporter, gemcitabine, drug transporter, transport protein
• Biological source: Vibrio cholerae serotype O1
• Total number of polymer chains: 1
• Total formula weight: 44920.60

Authors

Johnson, Z.L.,Lee, S.-Y. (deposition date: 2014-04-17, release date: 2014-08-13, Last modification date: 2023-09-27)

Primary citation

Johnson, Z.L.,Lee, J.H.,Lee, K.,Lee, M.,Kwon, D.Y.,Hong, J.,Lee, S.Y.
Structural basis of nucleoside and nucleoside drug selectivity by concentrative nucleoside transporters.
Elife, 3:e03604-e03604, 2014

PubMed Abstract: 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.

PubMed: 25082345
DOI: 10.7554/eLife.03604

Experimental method

X-RAY DIFFRACTION (2.906 Å)