2n7f

Publication Abstract from PubMed

The muO-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 to MfVIA. This analogue had increased potency at NaV1.8 and was analgesic in the mouse formalin assay.

Development of a muO-conotoxin Analogue with Improved Lipid Membrane Interactions and Potency for the Analgesic Target NaV1.8.,Deuis JR, Dekan Z, Inserra MC, Lee TH, Aguilar MI, Craik DJ, Lewis RJ, Alewood PF, Mobli M, Schroeder CI, Henriques ST, Vetter I J Biol Chem. 2016 Mar 29. pii: jbc.M116.721662. PMID:27026701^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.