A PARTICULARLY LABILE ASP-PRO BOND IN THE GREEN MAMBA MUSCARINIC TOXIN MTX2 - EFFECT OF PROTEIN CONFORMATION ON THE RATE OF CLEAVAGE

The single Asp(53)-pro(54) bond of the MTX2 toxin from the mamba snake Dendroaspis angusticeps is rapidly and efficiently cleaved in acidic solution (pH 1.5-2.5) at 45 degrees C, Unfolding of the toxin slows do wn the cleavage reaction by several times, Modelling studies indicate that the native toxin conformation can catalyse the Asp(53)-pro(54) bo nd cleavage, The implications of this study are: (i) cleavage of Asp-P ro bond for sequence determination may occur better in absence than in presence of denaturant, (ii) mild acid conditions, commonly used in N MR structure determinations, may irreversibly affect the structural in tegrity of Asp-Pro containing peptides and proteins.