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PDBsum entry 2epf
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References listed in PDB file
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Key reference
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Title
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Structures of pseudechetoxin and pseudecin, Two snake-Venom cysteine-Rich secretory proteins that target cyclic nucleotide-Gated ion channels: implications for movement of the c-Terminal cysteine-Rich domain.
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Authors
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N.Suzuki,
Y.Yamazaki,
R.L.Brown,
Z.Fujimoto,
T.Morita,
H.Mizuno.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2008,
64,
1034-1042.
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PubMed id
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Abstract
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Cyclic nucleotide-gated (CNG) ion channels play pivotal roles in sensory
transduction by retinal photoreceptors and olfactory neurons. The elapid snake
toxins pseudechetoxin (PsTx) and pseudecin (Pdc) are the only known protein
blockers of CNG channels. These toxins belong to a cysteine-rich secretory
protein (CRISP) family containing an N-terminal pathogenesis-related proteins of
group 1 (PR-1) domain and a C-terminal cysteine-rich domain (CRD). PsTx and Pdc
are highly homologous proteins, but their blocking affinities on CNG channels
are different: PsTx blocks both the olfactory and retinal channels with
approximately 15-30-fold higher affinity than Pdc. To gain further insights into
their structure and function, the crystal structures of PsTx, Pdc and Zn2+-bound
Pdc were determined. The structures revealed that most of the amino-acid-residue
differences between PsTx and Pdc are located around the concave surface formed
between the PR-1 domain and the CRD, suggesting that the concave surface is
functionally important for CNG-channel binding and inhibition. A structural
comparison in the presence and absence of Zn2+ ion demonstrated that the concave
surface can open and close owing to movement of the CRD upon Zn2+ binding. The
data suggest that PsTx and Pdc occlude the pore entrance and that the dynamic
motion of the concave surface facilitates interaction with the CNG channels.
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