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PDBsum entry 1c49
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Contents |
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* Residue conservation analysis
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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 and functional differences of two toxins from the scorpion pandinus imperator.
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Authors
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K.C.Klenk,
T.C.Tenenholz,
D.R.Matteson,
R.S.Rogowski,
M.P.Blaustein,
D.J.Weber.
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Ref.
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Proteins, 2000,
38,
441-449.
[DOI no: ]
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PubMed id
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Abstract
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The Pandinotoxins, PiTX-K alpha and PiTX-K beta, are members of the
Charybdotoxin family of scorpion toxins that can be used to characterize K+
channels. PiTX-K alpha differs from PiTX-K beta, another peptide from Pandinus
imperator, by one residue (P10E). When the two toxins are compared in a
physiological assay, the affinity of PiTX-K beta for voltage-gated, rapidly
inactivating K+ channels in dorsal root ganglia (DRG) neurons is 800-fold lower
than that of PiTX-K alpha (K alpha-IC50 = 8.0 nM versus K beta-IC50 = 6,500 nM).
To understand this difference, the three-dimensional structure of PiTX-K beta
was determined by nuclear magnetic resonance (NMR) spectroscopy and compared to
that of PiTX-K alpha. This comparison shows that structural differences between
the two toxins occur at a residue that is critical for blocking K+ channels
(K27) as well as at the site of the natural mutation (P10E). In PiTX-K beta, the
negatively charged carboxylate oxygen of E10 can approach the positive charge of
K27 and presumably reduces the net positive charge in this region of the toxin.
This is likely the reason why PiTX-K beta binds K+ channels from DRG neurons
with a much lower affinity than does PiTX-K alpha.
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Figure 1.
Figure 1. Chemical shift differences between PiTX-K  and
PiTX-K  .
The difference of the chemical shifts for all detected amide
(gray bars) and alpha (black bars) is shown as the absolute
value of PiTX-K minus
PiTX-K .
For side-chain protons, the absolute value of the largest
difference in the side chain is shown (striped bars), and
labeled appropriately.
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Figure 5.
Figure 5. pH dependence of the chemical shifts of the  protons
of E10 (  ,
 ),
the  protons
of K27 (  ),
and the protons
of K27 (  )
of PiTX-K .
These data are all consistent with a pK[a] of <3.5 for
protonation of E10 in PiTX-K .
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2000,
38,
441-449)
copyright 2000.
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Secondary reference #1
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Title
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Three new toxins from the scorpion pandinus imperator selectively block certain voltage-Gated k+ channels.
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Authors
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R.S.Rogowski,
J.H.Collins,
T.J.O'Neill,
T.A.Gustafson,
T.R.Werkman,
M.A.Rogawski,
T.C.Tenenholz,
D.J.Weber,
M.P.Blaustein.
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Ref.
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Mol Pharmacol, 1996,
50,
1167-1177.
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PubMed id
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