Tetanus and botulinum neurotoxins are produced by Clostridia and cause the neuroparalytic syndromes of tetanus and botulism. Tetanus neurotoxin acts mainly at the CNS synapse, while the seven botulinum neurotoxins act peripherally. Clostridial neurotoxins share a similar mechanism of cell intoxication: they block the release of neurotransmitters. They are composed of two disulfide-linked polypeptide chains. The larger subunit is responsible for neurospecific binding and cell penetration. Reduction releases the smaller chain in the neuronal cytosol, where it displays its zinc-endopeptidase activity specific for protein components of the neuroexocytosis apparatus. Tetanus neurotoxin and botulinum neurotoxins B, D, F and G recognize specifically VAMP/synaptobrevin. This integral protein of the synaptic vesicle membrane is cleaved at single peptide bonds, which differ for each neurotoxin. Botulinum A, and E neurotoxins recognize and cleave specifically SNAP-25, a protein of the presynaptic membrane, at two different sites within the carboxyl-terminus. Botulinum neurotoxin type C cleaves syntaxin, another protein of the nerve plasmalemma. These results indicate that VAMP, SNAP-25 a n d syntaxin play a central role in neuroexocytosis. These three proteins are conserved from yeast to humans and are essential in a variety of docking and fusion events in every cell. Tetanus and botulinum neurotoxins form a new group of zinc-endopeptidases with characteristic sequence, mode of zinc coordination, mechanism of activation and target recognition. They will be of great value in the unravelling of the mechanisms of exocytosis and endocytosis, as they are in the clinical treatment of dystonias.

Molecules built up from a given set of atoms may differ in their three-dimensional structure. They may have one or more asymmetric centres that serve as reference points for the steric distribution of the atoms. Carbon atoms, common to all biomolecules, are often such centres. For example, the Cα atom between the carboxyl and amino groups in amino acids is an asymmetric centre: looking ON ward (i.e. from the carbOxyl to the amiNo group, with the Cα oriented so that it is above the carboxyl and amino groups) the radical characterizing the amino acid may be to the right (D-molecules) or to the left (L-molecules). Nineteen of the 20 amino acids occurring in proteins have such a structure (the exception is glycine, where the radical is a hydrogen atom). These pairs of molecules cannot be brought into coincidence with their own mirror image, as is the situation with our hands. The phenomenon has therefore been named handedness, or chirality, from the Greek word cheir, meaning hand. The two forms of the chiral molecules are called enantiomers or antipodes. They differ in rotating the plane of the polarized light either to the right or to the left. The sense of rotation depends on the wavelength of the measuring light, but at a given wavelength it is always opposite for a pair of enantiomers. Chirality may also occur when achiral molecules form chiral substances during crystallization (for example, quartz forms D-quartz or Lquartz). A detailed theoretical treatment of molecular chirality is given by Barron (1991).