Molecular simulation reveals structural determinants of the hanatoxin binding in Kv2.1 channels

Yu Shuan Shiau, Tze Bin Lin, Horng Huey Liou, Po Tsarng Huang, Kuo Long Lou, Yuh Yuan Shiau

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The carboxyl terminus of the S3 segment (S3C) in voltage-gated potassium channels was suggested to be the binding site of gating modifier toxins like hanatoxin. It has also been proposed to have a helical secondary structural arrangement. The currently available structures in high resolution for such channel molecules are restricted to regions illustrating the pore function. Therefore no further direct experimental data to elucidate the detailed mechanism for such toxin binding can be derived. In order to examine the putative three-dimensional structure of S3C and to analyze the residues required for hanatoxin binding, molecular simulation and docking were performed, based on the solution structure of hanatoxin and the structural information from mutational scanning data for the S3C fragment in Kv2.1. Our results indicate that hydrophobic and electrostatic interactions are both utilized to stabilize the toxin binding. Precise docking residues and the appropriate orientation for binding regarding amphipathic environments are also described. Compared with the functional data proposed by previous studies, the helical structural arrangement for the C-terminus of the S3 segment in voltage-gated potassium channels can therefore be further emphasized and analyzed. The possible location/orientation for toxin binding with respect to membrane distribution around the S3C segment is also discussed in this paper.

Original languageEnglish
Pages (from-to)253-257
Number of pages5
JournalJournal of Molecular Modeling
Volume8
Issue number8
DOIs
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

determinants
Potassium
Voltage-Gated Potassium Channels
Electric potential
Binding sites
Molecular Docking Simulation
Coulomb interactions
simulation
Membranes
Scanning
Static Electricity
Hydrophobic and Hydrophilic Interactions
Molecules
Binding Sites
electric potential
fragments
hanatoxin
electrostatics
membranes
porosity

Keywords

  • Docking simulation
  • Hanatoxin binding
  • Kv2.1 (drk1)
  • S3 helix
  • Spatial freedom

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biophysics
  • Computer Science Applications
  • Computational Theory and Mathematics

Cite this

Molecular simulation reveals structural determinants of the hanatoxin binding in Kv2.1 channels. / Shiau, Yu Shuan; Lin, Tze Bin; Liou, Horng Huey; Huang, Po Tsarng; Lou, Kuo Long; Shiau, Yuh Yuan.

In: Journal of Molecular Modeling, Vol. 8, No. 8, 2002, p. 253-257.

Research output: Contribution to journalArticle

Shiau, Yu Shuan ; Lin, Tze Bin ; Liou, Horng Huey ; Huang, Po Tsarng ; Lou, Kuo Long ; Shiau, Yuh Yuan. / Molecular simulation reveals structural determinants of the hanatoxin binding in Kv2.1 channels. In: Journal of Molecular Modeling. 2002 ; Vol. 8, No. 8. pp. 253-257.
@article{eb6e4626c05a496b9ccc2bcee34c08f5,
title = "Molecular simulation reveals structural determinants of the hanatoxin binding in Kv2.1 channels",
abstract = "The carboxyl terminus of the S3 segment (S3C) in voltage-gated potassium channels was suggested to be the binding site of gating modifier toxins like hanatoxin. It has also been proposed to have a helical secondary structural arrangement. The currently available structures in high resolution for such channel molecules are restricted to regions illustrating the pore function. Therefore no further direct experimental data to elucidate the detailed mechanism for such toxin binding can be derived. In order to examine the putative three-dimensional structure of S3C and to analyze the residues required for hanatoxin binding, molecular simulation and docking were performed, based on the solution structure of hanatoxin and the structural information from mutational scanning data for the S3C fragment in Kv2.1. Our results indicate that hydrophobic and electrostatic interactions are both utilized to stabilize the toxin binding. Precise docking residues and the appropriate orientation for binding regarding amphipathic environments are also described. Compared with the functional data proposed by previous studies, the helical structural arrangement for the C-terminus of the S3 segment in voltage-gated potassium channels can therefore be further emphasized and analyzed. The possible location/orientation for toxin binding with respect to membrane distribution around the S3C segment is also discussed in this paper.",
keywords = "Docking simulation, Hanatoxin binding, Kv2.1 (drk1), S3 helix, Spatial freedom",
author = "Shiau, {Yu Shuan} and Lin, {Tze Bin} and Liou, {Horng Huey} and Huang, {Po Tsarng} and Lou, {Kuo Long} and Shiau, {Yuh Yuan}",
year = "2002",
doi = "10.1007/s00894-002-0095-8",
language = "English",
volume = "8",
pages = "253--257",
journal = "Journal of Molecular Modeling",
issn = "1610-2940",
publisher = "Springer Verlag",
number = "8",

}

TY - JOUR

T1 - Molecular simulation reveals structural determinants of the hanatoxin binding in Kv2.1 channels

AU - Shiau, Yu Shuan

AU - Lin, Tze Bin

AU - Liou, Horng Huey

AU - Huang, Po Tsarng

AU - Lou, Kuo Long

AU - Shiau, Yuh Yuan

PY - 2002

Y1 - 2002

N2 - The carboxyl terminus of the S3 segment (S3C) in voltage-gated potassium channels was suggested to be the binding site of gating modifier toxins like hanatoxin. It has also been proposed to have a helical secondary structural arrangement. The currently available structures in high resolution for such channel molecules are restricted to regions illustrating the pore function. Therefore no further direct experimental data to elucidate the detailed mechanism for such toxin binding can be derived. In order to examine the putative three-dimensional structure of S3C and to analyze the residues required for hanatoxin binding, molecular simulation and docking were performed, based on the solution structure of hanatoxin and the structural information from mutational scanning data for the S3C fragment in Kv2.1. Our results indicate that hydrophobic and electrostatic interactions are both utilized to stabilize the toxin binding. Precise docking residues and the appropriate orientation for binding regarding amphipathic environments are also described. Compared with the functional data proposed by previous studies, the helical structural arrangement for the C-terminus of the S3 segment in voltage-gated potassium channels can therefore be further emphasized and analyzed. The possible location/orientation for toxin binding with respect to membrane distribution around the S3C segment is also discussed in this paper.

AB - The carboxyl terminus of the S3 segment (S3C) in voltage-gated potassium channels was suggested to be the binding site of gating modifier toxins like hanatoxin. It has also been proposed to have a helical secondary structural arrangement. The currently available structures in high resolution for such channel molecules are restricted to regions illustrating the pore function. Therefore no further direct experimental data to elucidate the detailed mechanism for such toxin binding can be derived. In order to examine the putative three-dimensional structure of S3C and to analyze the residues required for hanatoxin binding, molecular simulation and docking were performed, based on the solution structure of hanatoxin and the structural information from mutational scanning data for the S3C fragment in Kv2.1. Our results indicate that hydrophobic and electrostatic interactions are both utilized to stabilize the toxin binding. Precise docking residues and the appropriate orientation for binding regarding amphipathic environments are also described. Compared with the functional data proposed by previous studies, the helical structural arrangement for the C-terminus of the S3 segment in voltage-gated potassium channels can therefore be further emphasized and analyzed. The possible location/orientation for toxin binding with respect to membrane distribution around the S3C segment is also discussed in this paper.

KW - Docking simulation

KW - Hanatoxin binding

KW - Kv2.1 (drk1)

KW - S3 helix

KW - Spatial freedom

UR - http://www.scopus.com/inward/record.url?scp=0036979653&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036979653&partnerID=8YFLogxK

U2 - 10.1007/s00894-002-0095-8

DO - 10.1007/s00894-002-0095-8

M3 - Article

VL - 8

SP - 253

EP - 257

JO - Journal of Molecular Modeling

JF - Journal of Molecular Modeling

SN - 1610-2940

IS - 8

ER -