Residue 54 has been shown to be important for bioactivity in several toxins. However, its role in the antinociceptive activity of toxins has not been evaluated yet. In this study, site-directed mutagenesis and mouse acetic acid writhing test were used to investigate the role of Ser54 in the antinociceptive activity of BmK9 neurotoxin from the Buthus martensii Karsch scorpion. Detailed mutagenesis analysis revealed that substitution of Ser54 by various polar amino acids produced no significant change in the antinociceptive activity, while all substitutions of nonpolar amino acid for Ser54 led to a significant loss of antinociceptive activity. Following the conformational analysis, it was suggested that Ser54 in BmK9 plays a functional role in the antinociceptive activity, the residue exerts its effect by means of a side-chain hydrogen bond.
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