CRYSTALLOGRAPHIC AND SPECTROSCOPIC CHARACTERIZATION OF A MOLECULAR HINGE - CONFORMATIONAL-CHANGES IN BOTHROPSTOXIN-I, A DIMERIC LYS49 PHOSPHOLIPASE-A2 HOMOLOG

Bothropstoxin I(BthTX-I) from the venom of Bothrops jararacussu is a m yotoxic phospholipase A2 (PLA2) homologue which, although catalyticall y inactive due to an Asp49-->Lys substitution, disrupts the integrity of lipid membranes by a Ca2+-independent mechanism, The crystal struct ures of two dimeric farms of BthLTX-I which diffract X-rays eo resolut ions of 3.1 and 2.1 Angstrom have been determined, The monomers in bot h structures are related by an almost perfect twofold axis of rotation and the dimer interfaces are defined by contacts between the N-termin al alpha-helical regions and the tips of the beta-wings of partner mon omers. Significant differences in the relative orientation of the mono mers in the two crystal forms results in ''open'' and ''closed'' dimer conformations, Spectroscopic Investigations of BthTX-I in solution ha ve correlated these conformational differences with changes in the int rinsic fluorescence emission of the single tryptophan residues located at the dimer interface, The possible relevance of this structural tra nsition in the Ca2+-independent membrane damaging activity is discusse d. (C) 1998 Wiley-Liss, Inc.