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* Residue conservation analysis
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PDB id:
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Metal transport, membrane protein
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Title:
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Nmr structural studies of a potassium channel / charybdotoxin complex
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Structure:
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Voltage-gated potassium channel. Chain: a, b, c, d. Engineered: yes. Mutation: yes. Charybdotoxin. Chain: e. Engineered: yes
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Source:
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Streptomyces lividans. Organism_taxid: 1916. Gene: kcsa, skc1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes
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NMR struc:
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1 models
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Authors:
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L.Yu,C.Sun,D.Song,J.Shen,N.Xu,A.Gunasekera,P.J.Hajduk,E.T.Olejniczak
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Key ref:
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L.Yu
et al.
(2005).
Nuclear magnetic resonance structural studies of a potassium channel-charybdotoxin complex.
Biochemistry,
44,
15834-15841.
PubMed id:
DOI:
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Date:
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11-Jul-05
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Release date:
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10-Jan-06
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PROCHECK
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Headers
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References
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DOI no:
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Biochemistry
44:15834-15841
(2005)
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PubMed id:
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Nuclear magnetic resonance structural studies of a potassium channel-charybdotoxin complex.
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L.Yu,
C.Sun,
D.Song,
J.Shen,
N.Xu,
A.Gunasekera,
P.J.Hajduk,
E.T.Olejniczak.
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ABSTRACT
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Ion channels play critical roles in signaling processes and are attractive
targets for treating various diseases. Here we describe an NMR-based strategy
for structural analyses of potassium channel-ligand complexes using KcsA
(residues 1-132, with six mutations to impart toxin binding and to mimic the
eukaryotic hERG channel). Using this approach, we determined the solution
structure of KcsA in complex with the high-affinity peptide antagonist
charybdotoxin. The structural data reveal how charybdotoxin binds to the closed
form of KcsA and makes specific contacts with the extracellular surface of the
ion channel, resulting in pore blockage. This represents the first direct
structural information about an ion channel complexed to a peptide antagonist
and provides an experimental framework for understanding and interpreting
earlier mutational analyses. The strategy presented here overcomes many of the
limitations of conventional NMR approaches to helical membrane protein structure
determination and can be applied in the study of the binding of druglike
molecules to this important class of proteins.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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C.J.Bohlen,
A.Priel,
S.Zhou,
D.King,
J.Siemens,
and
D.Julius
(2010).
A bivalent tarantula toxin activates the capsaicin receptor, TRPV1, by targeting the outer pore domain.
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Cell,
141,
834-845.
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G.A.Cook,
and
S.J.Opella
(2010).
NMR studies of p7 protein from hepatitis C virus.
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Eur Biophys J,
39,
1097-1104.
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H.J.Kim,
S.C.Howell,
W.D.Van Horn,
Y.H.Jeon,
and
C.R.Sanders
(2009).
Recent Advances in the Application of Solution NMR Spectroscopy to Multi-Span Integral Membrane Proteins.
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Prog Nucl Magn Reson Spectrosc,
55,
335-360.
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N.Y.Yount,
D.Kupferwasser,
A.Spisni,
S.M.Dutz,
Z.H.Ramjan,
S.Sharma,
A.J.Waring,
and
M.R.Yeaman
(2009).
Selective reciprocity in antimicrobial activity versus cytotoxicity of hBD-2 and crotamine.
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Proc Natl Acad Sci U S A,
106,
14972-14977.
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P.C.Chen,
and
S.Kuyucak
(2009).
Mechanism and energetics of charybdotoxin unbinding from a potassium channel from molecular dynamics simulations.
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Biophys J,
96,
2577-2588.
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C.Ader,
R.Schneider,
S.Hornig,
P.Velisetty,
E.M.Wilson,
A.Lange,
K.Giller,
I.Ohmert,
M.F.Martin-Eauclaire,
D.Trauner,
S.Becker,
O.Pongs,
and
M.Baldus
(2008).
A structural link between inactivation and block of a K+ channel.
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Nat Struct Mol Biol,
15,
605-612.
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C.Pimentel,
S.M'Barek,
V.Visan,
S.Grissmer,
F.Sampieri,
J.M.Sabatier,
H.Darbon,
and
Z.Fajloun
(2008).
Chemical synthesis and 1H-NMR 3D structure determination of AgTx2-MTX chimera, a new potential blocker for Kv1.2 channel, derived from MTX and AgTx2 scorpion toxins.
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Protein Sci,
17,
107-118.
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PDB code:
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H.Wulff,
and
B.S.Zhorov
(2008).
K+ channel modulators for the treatment of neurological disorders and autoimmune diseases.
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Chem Rev,
108,
1744-1773.
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K.Dougherty,
J.A.De Santiago-Castillo,
and
M.Covarrubias
(2008).
Gating charge immobilization in Kv4.2 channels: the basis of closed-state inactivation.
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J Gen Physiol,
131,
257-273.
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J.H.Chill,
J.M.Louis,
F.Delaglio,
and
A.Bax
(2007).
Local and global structure of the monomeric subunit of the potassium channel KcsA probed by NMR.
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Biochim Biophys Acta,
1768,
3260-3270.
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J.Hu,
H.Qin,
C.Li,
M.Sharma,
T.A.Cross,
and
F.P.Gao
(2007).
Structural biology of transmembrane domains: efficient production and characterization of transmembrane peptides by NMR.
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Protein Sci,
16,
2153-2165.
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S.F.Poget,
and
M.E.Girvin
(2007).
Solution NMR of membrane proteins in bilayer mimics: small is beautiful, but sometimes bigger is better.
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Biochim Biophys Acta,
1768,
3098-3106.
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S.H.Park,
and
S.J.Opella
(2007).
Conformational changes induced by a single amino acid substitution in the trans-membrane domain of Vpu: implications for HIV-1 susceptibility to channel blocking drugs.
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Protein Sci,
16,
2205-2215.
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PDB code:
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T.J.Morin,
and
W.R.Kobertz
(2007).
A derivatized scorpion toxin reveals the functional output of heteromeric KCNQ1-KCNE K+ channel complexes.
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ACS Chem Biol,
2,
469-473.
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A.Lange,
K.Giller,
S.Hornig,
M.F.Martin-Eauclaire,
O.Pongs,
S.Becker,
and
M.Baldus
(2006).
Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR.
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Nature,
440,
959-962.
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C.A.Ahern,
A.L.Eastwood,
H.A.Lester,
D.A.Dougherty,
and
R.Horn
(2006).
A cation-pi interaction between extracellular TEA and an aromatic residue in potassium channels.
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J Gen Physiol,
128,
649-657.
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C.R.Sanders,
and
F.Sönnichsen
(2006).
Solution NMR of membrane proteins: practice and challenges.
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Magn Reson Chem,
44,
S24-S40.
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C.Tang,
and
G.M.Clore
(2006).
A simple and reliable approach to docking protein-protein complexes from very sparse NOE-derived intermolecular distance restraints.
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J Biomol NMR,
36,
37-44.
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J.H.Chill,
J.M.Louis,
J.L.Baber,
and
A.Bax
(2006).
Measurement of 15N relaxation in the detergent-solubilized tetrameric KcsA potassium channel.
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J Biomol NMR,
36,
123-136.
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J.K.Rainey,
L.Fliegel,
and
B.D.Sykes
(2006).
Strategies for dealing with conformational sampling in structural calculations of flexible or kinked transmembrane peptides.
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Biochem Cell Biol,
84,
918-929.
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J.P.Bingham,
S.Bian,
Z.Y.Tan,
Z.Takacs,
and
E.Moczydlowski
(2006).
Synthesis of a biotin derivative of iberiotoxin: binding interactions with streptavidin and the BK Ca2+-activated K+ channel expressed in a human cell line.
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Bioconjug Chem,
17,
689-699.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
