Abstract:

LmKTT-1a is a dual-functional toxin recently discovered in scorpion venom glands. It has both protease and potassium ion channel inhibiting properties. Preliminary work has determined the solution structure of LmKTT-1a and evaluated its potassium ion channel inhibition function. In this study, NMR techniques and chemical shift perturbation analysis were used to identify the interaction interface between LmKTT-1a and the protease Trypsin. The residues of V10 to F17 in the loop region of LmKTT-1a was found to be the crucial binding sites. The NMR results were confirmed by a serious of mutations and enzymatic assays, and we found that K14 is the most pivotal residue in the interaction between Trypsin and LmKTT-1a. This work helped to further understand the structural-function relationship of LmKTT-1a.

Key words: NMR, interaction, chemical shift perturbation analysis, scorpion toxin, LmKTT-1a, trypsin