5lm0 | pdb_00005lm0

NMR spatial structure of Tk-hefu peptide

spinqualitylabelsall models 5lm0 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5lm0 is a 1 chain structure with sequence from Triticum kiharae. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function R4ZAN8_TRIKH Publication Abstract from PubMed Tk-hefu is an artificial peptide designed based on the a-hairpinin scaffold, which selectively blocks voltage-gated potassium channels Kv1.3. 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 Kv1.3 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 Kv1.3 selectivity and displays ~20 times greater activity compared to 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. Protein Surface Topography as a tool to enhance the selective activity of a potassium channel blocker.,Berkut AA, Chugunov AO, Mineev KS, Peigneur S, Tabakmakher VM, Krylov NA, Oparin PB, Lihonosova AF, Novikova EV, Arseniev AS, Grishin EV, Tytgat J, Efremov RG, Vassilevski AA J Biol Chem. 2019 Sep 18. pii: RA119.010494. doi: 10.1074/jbc.RA119.010494. PMID:31533989 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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