Three Dimensional Structures and Molecular Evolutions of Proteins I.
The Origin of Serine Proteases.


Faculty of Technology, Tokyo University of Agriculture and Technology.


Brenner(Natare. 334, 528 (1988)), analyzing their DNA sequences, proposed that serine proteases originate from a common ancester of cystein protease that existed billions of years ago. In the present study, we are going to discuss this problem in terms of 3 dimensional structures of proteases. Although similarities of amino acid sequences among 11 chymotrypsin family proteases are largely reduced, those in beta-barrel parts are well conserved relative to those in alpha-helices and coil parts. Molecular mechanics calculation of residue-residue interactions in beta-barrel parts indicated that specific inter-residue interactions stabilize beta-barrel structures in serine proteases. The pattern of inter-residue interactions in N-terminal beta-barrel parts is found to be appreciably different from that in C-terminal beta-barrel parts.

On the other hand, structural similarities between serine proteases and cystein proteases (papain and actinidin) are obscure in terms of both amino acid sequences and 3 dimensional local structures. The pattern of residue-residue interactions in beta-barrel structures of cystein proteases is fairly different from those of serine proteases. The present results do not give a direct support of Brenner's assumption and it seems that exquisite analyses of the evolution of tertiary structure formation mechanisms coupled with the evolution of amino acid sequences are needed.