Structural Basis of the Selective Block of Kv1.2 by Maurotoxin from Computer Simulations
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The 34-residue polypeptide maurotoxin (MTx) isolated from scorpion venoms selectively inhibits the current of the voltage-gated potassium channel Kv1.2 by occluding the ion conduction pathway. Here using molecular dynamics simulation as a docking method, the binding modes of MTx to three closely related channels (Kv1.1, Kv1.2 and Kv1.3) are examined. We show that MTx forms more favorable electrostatic interactions with the outer vestibule of Kv1.2 compared to Kv1.1 and Kv1.3, consistent with...[Show more]
dc.contributor.author | Chen, Rong | |
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dc.contributor.author | Chung, Shin-Ho | |
dc.date.accessioned | 2015-11-27T03:14:54Z | |
dc.date.available | 2015-11-27T03:14:54Z | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/1885/16864 | |
dc.description.abstract | The 34-residue polypeptide maurotoxin (MTx) isolated from scorpion venoms selectively inhibits the current of the voltage-gated potassium channel Kv1.2 by occluding the ion conduction pathway. Here using molecular dynamics simulation as a docking method, the binding modes of MTx to three closely related channels (Kv1.1, Kv1.2 and Kv1.3) are examined. We show that MTx forms more favorable electrostatic interactions with the outer vestibule of Kv1.2 compared to Kv1.1 and Kv1.3, consistent with the selectivity of MTx for Kv1.2 over Kv1.1 and Kv1.3 observed experimentally. One salt bridge in the bound complex of MTx-Kv1.2 forms and breaks in a simulation period of 20 ns, suggesting the dynamic nature of toxin-channel interactions. The toxin selectivity likely arises from the differences in the shape of the channel outer vestibule, giving rise to distinct orientations of MTx on block. Potential of mean force calculations show that MTx blocks Kv1.1, Kv1.2 and Kv1.3 with an IC(50) value of 6 µM, 0.6 nM and 18 µM, respectively. | |
dc.description.sponsorship | This work was supported by the National Health and Medical Research Council of Australia (http://www.nhmrc.gov.au). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | |
dc.publisher | Public Library of Science | |
dc.rights | © Chen, Chung. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |
dc.source | PLoS ONE | |
dc.source.uri | http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0047253 | |
dc.subject | amino acid sequence | |
dc.subject | binding sites | |
dc.subject | kv1.2 potassium channel | |
dc.subject | kv1.3 potassium channel | |
dc.subject | models, molecular | |
dc.subject | scorpion venoms | |
dc.subject | molecular dynamics simulation | |
dc.title | Structural Basis of the Selective Block of Kv1.2 by Maurotoxin from Computer Simulations | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 7 | |
dc.date.issued | 2012-10-10 | |
local.identifier.absfor | 030600 | |
local.identifier.ariespublication | f5625xPUB1439 | |
local.publisher.url | http://journals.plos.org/ | |
local.type.status | Published Version | |
local.contributor.affiliation | Chen, Rong, College of Medicine, Biology and Environment, CMBE Research School of Biology, Division of Biomedical Science and Biochemistry, The Australian National University | |
local.contributor.affiliation | Chung, Shin-Ho, College of Medicine, Biology and Environment, CMBE Research School of Biology, Division of Biomedical Science and Biochemistry, The Australian National University | |
local.identifier.essn | 1932-6203 | |
local.bibliographicCitation.issue | 10 | |
local.bibliographicCitation.startpage | e47253 | |
local.identifier.doi | 10.1371/journal.pone.0047253 | |
dc.date.updated | 2015-12-10T10:49:55Z | |
local.identifier.scopusID | 2-s2.0-84867391072 | |
local.identifier.thomsonID | 000312385200096 | |
Collections | ANU Research Publications |
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