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PDBsum entry 4pda
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Transport protein
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PDB id
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4pda
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References listed in PDB file
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Key reference
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Title
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Structural basis of nucleoside and nucleoside drug selectivity by concentrative nucleoside transporters.
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Authors
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Z.L.Johnson,
J.H.Lee,
K.Lee,
M.Lee,
D.Y.Kwon,
J.Hong,
S.Y.Lee.
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Ref.
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Elife, 2014,
3,
e03604.
[DOI no: ]
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PubMed id
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Abstract
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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.DOI:
http://dx.doi.org/10.7554/eLife.03604.001.
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