Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Biophys J
2003 May 01;845:3022-36. doi: 10.1016/S0006-3495(03)70028-9.
Show Gene links
Show Anatomy links
BeKm-1 is a HERG-specific toxin that shares the structure with ChTx but the mechanism of action with ErgTx1.
Zhang M
,
Korolkova YV
,
Liu J
,
Jiang M
,
Grishin EV
,
Tseng GN
.
???displayArticle.abstract???
Peptide toxins with disulfide-stabilized structures have been used as molecular calipers to probe the outer vestibule structure of K channels. We want to apply this approach to the human ether-a-go-go-related gene (HERG) channel, whose outer vestibule is unique in structure and function among voltage-gated K channels. Our focus here is BeKm-1, a HERG-specific peptide toxin that can suppress HERG in the low nM concentration range. Although BeKm-1 shares the three-dimensional scaffold with the well-studied charybdotoxin, the two use different mechanisms in suppressing currents through their target K channels. BeKm-1 binds near, but not inside, the HERG pore, and it is possible that BeKm-1-bound HERG channels can conduct currents although with markedly altered voltage-dependence and kinetics of gating. BeKm-1 and ErgTx1 differ in three-dimensional scaffold, but the two share mechanism of action and have overlapping binding sites on the HERG channel. For both, residues in the middle of the S5-P linker (the putative 583-597 helix) and residues at the pore entrance are critical for binding, although specific contact points vary between the two. Toxin foot printing using BeKm-1 and ErgTx1 will likely provide complementary information about the unique outer vestibule structure of the HERG channel.
Capener,
Homology modeling and molecular dynamics simulation studies of an inward rectifier potassium channel.
2000, Pubmed
Capener,
Homology modeling and molecular dynamics simulation studies of an inward rectifier potassium channel.
2000,
Pubmed
Cestèle,
Voltage sensor-trapping: enhanced activation of sodium channels by beta-scorpion toxin bound to the S3-S4 loop in domain II.
1998,
Pubmed
Chen,
Position of aromatic residues in the S6 domain, not inactivation, dictates cisapride sensitivity of HERG and eag potassium channels.
2002,
Pubmed
,
Xenbase
Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed
Faravelli,
A HERG-like K+ channel in rat F-11 DRG cell line: pharmacological identification and biophysical characterization.
1996,
Pubmed
Goldstein,
The charybdotoxin receptor of a Shaker K+ channel: peptide and channel residues mediating molecular recognition.
1994,
Pubmed
,
Xenbase
Goldstein,
Mechanism of charybdotoxin block of a voltage-gated K+ channel.
1993,
Pubmed
,
Xenbase
Gross,
Agitoxin footprinting the shaker potassium channel pore.
1996,
Pubmed
,
Xenbase
Gurrola,
A toxin to nervous, cardiac, and endocrine ERG K+ channels isolated from Centruroides noxius scorpion venom.
1999,
Pubmed
Hidalgo,
Revealing the architecture of a K+ channel pore through mutant cycles with a peptide inhibitor.
1995,
Pubmed
,
Xenbase
Jiang,
Mechanism for the effects of extracellular acidification on HERG-channel function.
1999,
Pubmed
,
Xenbase
Jiang,
The open pore conformation of potassium channels.
2002,
Pubmed
Korolkova,
New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1.
2002,
Pubmed
Korolkova,
An ERG channel inhibitor from the scorpion Buthus eupeus.
2001,
Pubmed
Larsson,
A conserved glutamate is important for slow inactivation in K+ channels.
2000,
Pubmed
,
Xenbase
Lecchi,
Isolation of a long-lasting eag-related gene-type K+ current in MMQ lactotrophs and its accommodating role during slow firing and prolactin release.
2002,
Pubmed
Lipkind,
A model of scorpion toxin binding to voltage-gated K+ channels.
1997,
Pubmed
Li-Smerin,
Localization and molecular determinants of the Hanatoxin receptors on the voltage-sensing domains of a K(+) channel.
2000,
Pubmed
,
Xenbase
Li-Smerin,
Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels.
1998,
Pubmed
,
Xenbase
Liu,
Structural and functional role of the extracellular s5-p linker in the HERG potassium channel.
2002,
Pubmed
,
Xenbase
MacKinnon,
Mutant potassium channels with altered binding of charybdotoxin, a pore-blocking peptide inhibitor.
1989,
Pubmed
,
Xenbase
Miller,
The charybdotoxin family of K+ channel-blocking peptides.
1995,
Pubmed
Mitcheson,
Trapping of a methanesulfonanilide by closure of the HERG potassium channel activation gate.
2000,
Pubmed
,
Xenbase
Nastainczyk,
A short-chain peptide toxin isolated from Centruroides sculpturatus scorpion venom inhibits ether-à-go-go-related gene K(+) channels.
2002,
Pubmed
Numaguchi,
Probing the interaction between inactivation gating and Dd-sotalol block of HERG.
2000,
Pubmed
Pardo-Lopez,
Mapping the binding site of a human ether-a-go-go-related gene-specific peptide toxin (ErgTx) to the channel's outer vestibule.
2002,
Pubmed
Park,
Interaction of charybdotoxin with permeant ions inside the pore of a K+ channel.
1992,
Pubmed
Ranganathan,
Spatial localization of the K+ channel selectivity filter by mutant cycle-based structure analysis.
1996,
Pubmed
Rauer,
Structure-guided transformation of charybdotoxin yields an analog that selectively targets Ca(2+)-activated over voltage-gated K(+) channels.
2000,
Pubmed
Roche,
A virtual screening method for prediction of the HERG potassium channel liability of compound libraries.
2002,
Pubmed
Roden,
A plethora of mechanisms in the HERG-related long QT syndrome. Genetics meets electrophysiology.
1999,
Pubmed
Rosati,
Glucose- and arginine-induced insulin secretion by human pancreatic beta-cells: the role of HERG K(+) channels in firing and release.
2000,
Pubmed
Sanguinetti,
A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel.
1995,
Pubmed
,
Xenbase
Smith,
Functional up-regulation of HERG K+ channels in neoplastic hematopoietic cells.
2002,
Pubmed
Smith,
The inward rectification mechanism of the HERG cardiac potassium channel.
1996,
Pubmed
Spector,
Fast inactivation causes rectification of the IKr channel.
1996,
Pubmed
,
Xenbase
Stocker,
Electrostatic distance geometry in a K+ channel vestibule.
1994,
Pubmed
,
Xenbase
Swartz,
Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K+ channels.
1997,
Pubmed
Swartz,
Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites.
1997,
Pubmed
,
Xenbase
Torres,
Solution structure of CnErg1 (Ergtoxin), a HERG specific scorpion toxin.
2003,
Pubmed
Trudeau,
HERG, a human inward rectifier in the voltage-gated potassium channel family.
1995,
Pubmed
Tseng,
I(Kr): the hERG channel.
2001,
Pubmed
Tytgat,
A unified nomenclature for short-chain peptides isolated from scorpion venoms: alpha-KTx molecular subfamilies.
1999,
Pubmed
Ulens,
Redox state dependency of HERGS631C channel pharmacology: relation to C-type inactivation.
2000,
Pubmed
,
Xenbase
Wang,
Modulation of HERG affinity for E-4031 by [K+]o and C-type inactivation.
1997,
Pubmed
,
Xenbase
Wang,
MinK residues line a potassium channel pore.
1996,
Pubmed
Zhou,
HERG-like K+ channels in microglia.
1998,
Pubmed
