STRUCTURE AND MECHANISM OF A SUBFAMILY OF ENZYMES RELATED TO N-ACETYLNEURAMINATE LYASE

We describe here a sub-family of enzymes related both structurally and functionally to N-acetylneuraminate lyase. Two members of this family (N-acetylneuraminate lyase and dihydrodipicolinate synthase) have kno wn three-dimensional structures and we now proceed to show their struc tural and functional relationship to two further proteins, trans-o-hyd roxybenzylidenepyruvate hydratase-aldolase and D-4-deoxy-5-oxoglucarat e dehydratase. These enzymes are all thought to involve intermediate S chiff-base formation with their respective substrates. In order to und erstand the nature of this intermediate, we have determined the three- dimensional structure of N-acetylneuraminate lyase in complex with hyd roxypyruvate (a product analogue) and in complex with one of its produ cts (pyruvate). From these structures we deduce the presence of a clos ely similar Schiff-base forming motif in all members of the N-acetylne uraminate lyase sub-family. A fifth protein, MosA, is also confirmed t o be a member of the sub-family although the involvement of an interme diate Schiff-base in its proposed reaction is unclear. (C) 1997 Academ ic Press Limited.