Structure of a new neurotoxin from the scorpion Buthus martensii Karsch at1.76 angstrom

A new neurotoxin BmK M2, toxic to both mammals and insects, with the strong est toxicity in the BmK toxin series, has been purified from the Chinese sc orpion Buthus martensii Karsch and crystallized with MPD at pH 7.5. The cry stals are orthorhombic, belonging to space group P2(1)2(1)2(1), with unit-c ell parameters a = 36.64, b = 36.95, c = 37.23 Angstrom. The structure was solved by molecular replacement and refined to R = 0.186 for all reflection s to a resolution of 1.76 Angstrom. The whole sequence (64 residues) of BmK M2 was determined by crystallographic analysis based on high-resolution da ta and the homologous model of BmK M8. The refined BmK M2 structure shows a non-proline cis peptide bond between Pro9 and His10 which enables the C-te rminal segment to adopt a conformation different to that of the weak toxin BmK M8. Recently, a mutation analysis had suggested that both the tenth res idue and the C-terminus play key roles in receptor binding. Therefore, thes e features may be related to the binding selectivity of the group III alpha -like toxins. The charge changes of residues 8, 10, 18, 28, 55 and 59 from neutral or negative to positive or neutral, which leads to a positive elect rostatic potential surface, may be responsible for the high toxicity of BmK M2.