The molecular peculiarities of catalase-peroxidases

In developing ideas of how protein structure modifies haem reactivity, the activity of Class I of the plant peroxidase superfamily (including cytochro me c peroxidase, ascorbate peroxidase and catalase-peroxidases (KatGs)) is an exciting field of research. Despite striking sequence homologies, there are dramatic differences in catalytic activity and substrate specificity wi th KatGs being the only member with substantial catalase activity. Based on multiple sequence alignment performed for Class I peroxidases, we present a hypothesis for the pronounced catalase activity of KatGs. In their cataly tic domains KatGs are shown to possess three large insertions, two of them are typical for KatGs showing highly conserved sequence patterns. Besides a n extra C-terminal copy of the ancestral hydroperoxidase gene resulting fro m gene duplication, these two large loops are likely to control the orienta tion of both the haem group and of essential residues in the active site. T hey seem to modulate the access of substrates to the prosthetic group at th e distal side as well as the flexibility and character of the bond between the proximal histidine and the ferric iron. The hypothesis presented opens new possibilities in the rational engineering of peroxidases. (C) 2001 Fede ration of European Biochemical Societies, Published by Elsevier Science B.V . All rights reserved.