5LM0

NMR spatial structure of Tk-hefu peptide

Summary for 5LM0

• Entry DOI: 10.2210/pdb5lm0/pdb
• NMR Information: BMRB: 34027
• Descriptor: L-2 (1 entity in total)
• Functional Keywords: protein mutant plant defense peptide, protein, anti microbial protein, antimicrobial protein
• Biological source: Triticum kiharae (Wheat)
• Total number of polymer chains: 1
• Total formula weight: 3565.08

Authors

Mineev, K.S.,Berkut, A.A.,Novikova, E.V.,Oparin, P.B.,Grishin, E.V.,Arseniev, A.S.,Vassilevski, A.A. (deposition date: 2016-07-28, release date: 2017-08-16, Last modification date: 2024-11-13)

Primary citation

Berkut, A.A.,Chugunov, A.O.,Mineev, K.S.,Peigneur, S.,Tabakmakher, V.M.,Krylov, N.A.,Oparin, P.B.,Lihonosova, A.F.,Novikova, E.V.,Arseniev, A.S.,Grishin, E.V.,Tytgat, J.,Efremov, R.G.,Vassilevski, A.A.
Protein Surface Topography as a tool to enhance the selective activity of a potassium channel blocker.
J.Biol.Chem., 2019

PubMed Abstract: Tk-hefu is an artificial peptide designed based on the α-hairpinin scaffold, which selectively blocks voltage-gated potassium channels K1.3. Here we present its spatial structure resolved by NMR spectroscopy and analyze its interaction with channels using computer modeling. We apply protein surface topography to suggest mutations and increase Tk-hefu affinity to the K1.3 channel isoform. We redesign the functional surface of Tk-hefu to better match the respective surface of the channel pore vestibule. The resulting peptide Tk-hefu-2 retains K1.3 selectivity and displays ∼15 times greater activity compared with Tk-hefu. We verify the mode of Tk-hefu-2 binding to the channel outer vestibule experimentally by site-directed mutagenesis. We argue that scaffold engineering aided by protein surface topography represents a reliable tool for design and optimization of specific ion channel ligands.

PubMed: 31533989
DOI: 10.1074/jbc.RA119.010494

Experimental method

SOLUTION NMR