1ZVE

Crystal Structure Of Mutant K8G Of Scorpion alpha-Like Neurotoxin Bmk M1 From Buthus Martensii Karsch

Summary for 1ZVE

• Entry DOI: 10.2210/pdb1zve/pdb
• Related: 1ZU3 1ZUT 1ZVG
• Descriptor: Alpha-like neurotoxin BmK-I, ACETATE ION (3 entities in total)
• Functional Keywords: scorpion alpha-like toxin, bmk m1, mutant, mammal/insect selectivity, toxin
• Biological source: Mesobuthus martensii (Chinese scorpion)
• Cellular location: Secreted: P45697
• Total number of polymer chains: 1
• Total formula weight: 7423.37

Authors

Ye, X.,Bosmans, F.,Li, C.,Zhang, Y.,Wang, D.C.,Tytgat, J. (deposition date: 2005-06-01, release date: 2006-05-23, Last modification date: 2024-11-06)

Primary citation

Ye, X.,Bosmans, F.,Li, C.,Zhang, Y.,Wang, D.C.,Tytgat, J.
Structural basis for the voltage-gated Na+ channel selectivity of the scorpion alpha-like toxin BmK M1
J.Mol.Biol., 353:788-803, 2005

PubMed Abstract: Scorpion alpha-like toxins are proteins that act on mammalian and insect voltage-gated Na+ channels. Therefore, these toxins constitute an excellent target for examining the foundations that underlie their target specificity. With this motive we dissected the role of six critical amino acids located in the five-residue reverse turn (RT) and C-tail (CT) of the scorpion alpha-like toxin BmK M1. These residues were individually substituted resulting in 11 mutants and were subjected to a bioassay on mice, an electrophysiological characterization on three cloned voltage-gated Na+ channels (Nav1.2, Nav1.5 and para), a CD analysis and X-ray crystallography. The results reveal two molecular sites, a couplet of residues (8-9) in the RT and a hydrophobic surface consisting of residues 57 and 59-61 in the CT, where the substitution with specific residues can redirect the alpha-like characteristics of BmK M1 to either total insect or much higher mammal specificity. Crystal structures reveal that the pharmacological ramification of these mutants is accompanied by the reshaping of the 3D structure surrounding position 8. Furthermore, our results also reveal that residues 57 and 59-61, located at the CT, enclose the critical residue 58 in order to form a hydrophobic "gasket". Mutants of BmK M1 that interrupt this hydrophobic surface significantly gain insect selectivity.

PubMed: 16209876
DOI: 10.1016/j.jmb.2005.08.068

Experimental method

X-RAY DIFFRACTION (1.7 Å)