2N7F

NMR solution structure of muO-conotoxin MfVIA

2N7F の概要

• エントリーDOI: 10.2210/pdb2n7f/pdb
• NMR情報: BMRB: 25804
• 分子名称: muO-conotoxin MfVIA (1 entity in total)
• 機能のキーワード: muo-conotoxin, diulfide-rich, toxin
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3656.41

構造登録者

Schroeder, C.I.,Mobli, M. (登録日: 2015-09-09, 公開日: 2016-04-06, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

SOLUTION NMR