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PDBsum entry 1lmm
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References listed in PDB file
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Key reference
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Title
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Recombinant production and solution structure of pctx1, The specific peptide inhibitor of asic1a proton-Gated cation channels.
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Authors
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P.Escoubas,
C.Bernard,
G.Lambeau,
M.Lazdunski,
H.Darbon.
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Ref.
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Protein Sci, 2003,
12,
1332-1343.
[DOI no: ]
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PubMed id
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Abstract
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Acid-sensing ion channels (ASICs) are thought to be important ion channels,
particularly for the perception of pain. Some of them may also contribute to
synaptic plasticity, learning, and memory. Psalmotoxin 1 (PcTx1), the first
potent and specific blocker of the ASIC1a proton-sensing channel, has been
successfully expressed in the Drosophila melanogaster S2 cell recombinant
expression system used here for the first time to produce a spider toxin. The
recombinant toxin was identical in all respects to the native peptide, and its
three-dimensional structure in solution was determined by means of (1)H 2D NMR
spectroscopy. Surface characteristics of PcTx1 provide insights on key
structural elements involved in the binding of PcTx1 to ASIC1a channels. They
appear to be localized in the beta-sheet and the beta-turn linking the strands,
as indicated by electrostatic anisotropy calculations, surface charge
distribution, and the presence of residues known to be implicated in channel
recognition by other inhibitor cystine knot (ICK) toxins.
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Figure 4.
Figure 4. (A) Stereoview of the best fit of 20 solution
structures of PcTx1. C[  ]are shown.
The N and C termini are labeled "N" and "C". (B) Molecular
surface colored according to the electrostatic charge (red for
acidic and blue for basic) and the resulting dipolar moment (red
arrow). The aromatic residues are indicated and colored in
purple. (C) CPK representation of the proposed functional
surface of PcTx1. The residues suspected to be important for the
interaction of the toxin with the channel are labeled. Residues
are colored as follows: green for polar uncharged residues, blue
for basic residues, red for acidic residues, purple for aromatic
residues, and yellow for aliphatic residues.
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Figure 6.
Figure 6. Comparison of putative functional dyads of PcTx1
(A) and related ICK toxins J-atracotoxin Hv1c (PDB 1DL0 [PDB]
; B),  -conotoxin
PVIIA (PDB 1KCP [PDB]
; C), and agitoxin 2 (PDB 1AGT [PDB]
; D). Basic residues side chains are colored in blue; aromatic
residues side chains, in orange.
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The above figures are
reprinted
by permission from the Protein Society:
Protein Sci
(2003,
12,
1332-1343)
copyright 2003.
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