Development of a ?O-Conotoxin Analogue with Improved Lipid Membrane Interactions and Potency for the Analgesic Sodium Channel NaV1.8.
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ABSTRACT:
SUBMITTER: Deuis JR
PROVIDER: S-EPMC4882450 | biostudies-literature | 2016 May
REPOSITORIES: biostudies-literature
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Development of a μO-Conotoxin Analogue with Improved Lipid Membrane Interactions and Potency for the Analgesic Sodium Channel NaV1.8.
Deuis Jennifer R JR Dekan Zoltan Z Inserra Marco C MC Lee Tzong-Hsien TH Aguilar Marie-Isabel MI Craik David J DJ Lewis Richard J RJ Alewood Paul F PF Mobli Mehdi M Schroeder Christina I CI Henriques Sónia Troeira ST Vetter Irina I
The Journal of biological chemistry 20160329 22
The μO-conotoxins MrVIA, MrVIB, and MfVIA inhibit the voltage-gated sodium channel NaV1.8, a well described target for the treatment of pain; however, little is known about the residues or structural elements that define this activity. In this study, we determined the three-dimensional structure of MfVIA, examined its membrane binding properties, performed alanine-scanning mutagenesis, and identified residues important for its activity at human NaV1.8. A second round of mutations resulted in (E5 ...[more]
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