The investigation of interactions of κ-Hefutoxin1 with the voltage-gated potassium channels: A computational simulation

• Published in: Proteins, structure, function, and bioinformatics structure, function, and bioinformatics, 2008-05, Vol.71 (3), p.1441-1449
• Main Authors: Zarrabi, M., Naderi-Manesh, H.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Computational Biology - methods; computational simulation; Computer Simulation; docking; Humans; interactions; Kv1.1 Potassium Channel - chemistry; Kv1.1 Potassium Channel - metabolism; Kv1.2 Potassium Channel - chemistry; Kv1.2 Potassium Channel - metabolism; Kv1.3 Potassium Channel - chemistry; Kv1.3 Potassium Channel - metabolism; Molecular Sequence Data; potassium channel; Protein Binding; scorpion toxin; Scorpion Venoms - chemistry; Scorpion Venoms - metabolism; κ-Hefutoxin1
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/prot.21833

κ‐Hefutoxin1 is a K+ channel‐blocking toxin from the scorpion Heterometrus fluvipes. It is a 22‐residue protein that adapts a novel fold of two parallel helices linked by two disulfide bridges without β‐sheets. Recognition of interactions of κ‐Hefutoxin1 with the voltage‐gated potassium channels, Kv1.1, Kv1.2, and Kv1.3, was studied by 3D‐Dock software package. All structures of κ‐Hefutoxin1 were considered during the simulations, which indicated that even small changes in the structure of κ‐Hefutoxin1 considerably affected both the recognition and the binding between κ‐Hefutoxin1 and the Kv1 channels. κ‐Hefutoxin1 is located around the extracellular part of the Kv1 channels, making contacts with its helices. Lys 19, Tyr 5, Arg 6, Trp 9, or Arg 10 in the toxin and residues Asp 402, His 404, Thr 407,Gly 401, and Asp 386 in each subunit of the Kv potassium channel are the key residues for the toxin‐channel recognition. Moreover, the simulation result demonstrates that the hydrophobic interactions are important in interaction of negatively charged toxins with potassium channels. The results of our docking/molecular dynamics simulations indicate that our 3D model structure of the κ‐Hefutoxin1‐complex is both reasonable and acceptable and could be helpful for smarter drug design and the blocking agents of Kv1 channels. Proteins 2008. © 2007 Wiley‐Liss, Inc.