2N7F

NMR solution structure of muO-conotoxin MfVIA

Summary for 2N7F

• Entry DOI: 10.2210/pdb2n7f/pdb
• NMR Information: BMRB: 25804
• Descriptor: muO-conotoxin MfVIA (1 entity in total)
• Functional Keywords: muo-conotoxin, diulfide-rich, toxin
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 3656.41

Authors

Schroeder, C.I.,Mobli, M. (deposition date: 2015-09-09, release date: 2016-04-06, Last modification date: 2024-10-30)

Primary citation

Deuis, J.R.,Dekan, Z.,Inserra, M.C.,Lee, T.H.,Aguilar, M.I.,Craik, D.J.,Lewis, R.J.,Alewood, P.F.,Mobli, M.,Schroeder, C.I.,Henriques, S.T.,Vetter, I.
Development of a mu O-Conotoxin Analogue with Improved Lipid Membrane Interactions and Potency for the Analgesic Sodium Channel NaV1.8.
J.Biol.Chem., 291:11829-11842, 2016

PubMed Abstract: 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 (E5K,E8K)MfVIA, a double mutant with greater positive surface charge and greater affinity for lipid membranes compared with MfVIA. This analogue had increased potency at NaV1.8 and was analgesic in the mouse formalin assay.

PubMed: 27026701
DOI: 10.1074/jbc.M116.721662

Experimental method

SOLUTION NMR