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PDBsum entry 4ro2
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Transport protein
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PDB id
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4ro2
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References listed in PDB file
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Key reference
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Title
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A structural, Functional, And computational analysis suggests pore flexibility as the base for the poor selectivity of cng channels.
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Authors
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L.M.Napolitano,
I.Bisha,
M.De march,
A.Marchesi,
M.Arcangeletti,
N.Demitri,
M.Mazzolini,
A.Rodriguez,
A.Magistrato,
S.Onesti,
A.Laio,
V.Torre.
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Ref.
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Proc Natl Acad Sci U S A, 2015,
112,
E3619.
[DOI no: ]
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PubMed id
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Abstract
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Cyclic nucleotide-gated (CNG) ion channels, despite a significant homology with
the highly selective K(+) channels, do not discriminate among monovalent alkali
cations and are permeable also to several organic cations. We combined
electrophysiology, molecular dynamics (MD) simulations, and X-ray
crystallography to demonstrate that the pore of CNG channels is highly flexible.
When a CNG mimic is crystallized in the presence of a variety of monovalent
cations, including Na(+), Cs(+), and dimethylammonium (DMA(+)), the side chain
of Glu66 in the selectivity filter shows multiple conformations and the diameter
of the pore changes significantly. MD simulations indicate that Glu66 and the
prolines in the outer vestibule undergo large fluctuations, which are modulated
by the ionic species and the voltage. This flexibility underlies the coupling
between gating and permeation and the poor ionic selectivity of CNG channels.
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