RELATIONSHIPS BETWEEN STRUCTURE AND ACTIVITY IN THE ALPHA-AMYLASE FAMILY OF STARCH-METABOLIZING ENZYMES

Alpha-amylases are known to be multidomain proteins, i. e., the molecules consist of several folding units. Each alpha-amylase is believed, however, to have a catalytic domain consisting of a barrel of eight parallel beta-strands surrounded by eight alpha-helices, with an extra helix inserted after the sixth beta-strand. The beta-strands and helices alternate along the polypeptide chain and are linked together by irregular loops. Amino acid residues situated on the loops joining the C-terminal end of each beta-strand to the N-terminal end of the following helix make up the active site of the enzymes. A similar structure has been found in cyclodextrin glucanotransferases and it is now believed that such a (beta/alpha)8-barrel also constitutes the catalytic domain of enzymes active on alpha-1,6-glucosidic bonds, and of enzymes with dual specificity for both alpha-1,4- and alpha-1,6- bonds. Knowledge of the three-dimensional structure of alpha-amylases and cyclodextrin glucanotransferase has made possible identification of structural features important for enzymic activity and specificity. By analogy, some general conclusions are reached concerning pullulanase, isoamylase, oligo-1,6-glucosidase, neopullulanase and branching enzymes.