Energy minimization for tertiary structure prediction of homologous proteins: alpha 1-purothionin and viscotoxin A3 models from crambin.

Abstract

Homologous proteins may fold into similar three-dimensional structures. Spectroscopic evidence suggests this is true for the cereal grain thionins, the mistletoe toxins, and for crambin, three classes of plant proteins. We have combined primary sequence homology and energy minimization to predict the structures alpha 1-purothionin (from Durum wheat) and viscotoxin A3 (from Viscum album, European mistletoe) from the high resolution (0.945 A) crystal structure of crambin (from Crambe abyssinica). Our predictions will be verifiable because we have diffraction-quality crystals of alpha 1-purothionin whose structure we are have predicted. The potential energy minimizations for each protein were performed both with and without harmonic constraints to its initial backbone to explore the existence of local minima for the predicted proteins. Crambin was run as a control to examine the effects of the potential energy minimization on a protein with a well-known structure. Only alpha 1-purothionin which has one fewer residue in a turn region shows a significant difference for the two minimization paths. The results of these predictions suggest that alpha 1-purothionin and viscotoxin are amphipathic proteins, and this character may relate to the mechanism of action for these proteins. Both are mildly membrane-active and their amphipatic character is well suited for interaction with a lipid bilayer.