Protein similarities beyond disulphide bridge topology

Structural superimposition is an important procedure to analyse the relatio nships between proteins. A new approach and program, KNOT-MATCH, has been d eveloped for automated structural superimposition of proteins by means of t heir disulphide bridge topology. As a result of the superimposition, regula r secondary structures, loops and clusters of residues become correctly ali gned. This fact allows us to find out important structural overlaps of resi dues, sometimes with functional significance, not only among proteins belon ging to the same family but also between apparently non-related proteins. D ifferent disulphide-rich protein families, such as EGF-like, defensin-like and plant protease inhibitors, have been self or cross analysed with this a pproach. Some amino acids that have been experimentally determined to be st ructural and/or functional key residues for these proteins are conserved in the three-dimensional space after superimposition by KNOT-MATCH. The progr am can be very useful for finding relationships among proteins that would b e hidden to the current alignment methods based on sequence and on main-cha in topology. (C) 1998 Academic Press.