The structures of enzymes catalyzing the reactions in central
metabolic pathways are generally well conserved as are their
catalytic mechanisms. The two types of 3-dehydroquinate
dehydratase (DHQase) are therefore most unusual since they
are unrelated at the sequence level and they utilize completely
different mechanisms to catalyze the same overall reaction.
The type I enzymes catalyze a cis-dehydration of 3-dehydroquinate
via a covalent imine intermediate, while the type II
enzymes catalyze a trans-dehydration via an enolate intermediate.
Here we report the three-dimensional structures of a
representative member of each type of biosynthetic DHQase.Both enzymes function as part of the shikimate pathway,
which is essential in microorganisms and plants for the
biosynthesis of aromatic compounds including folate,
ubiquinone and the aromatic amino acids. An explanation for
the presence of two different enzymes catalyzing the same
reaction is presented. The absence of the shikimate pathway in
animals makes it an attractive target for antimicrobial agents.
The availability of these two structures opens the way for the
design of highly specific enzyme inhibitors with potential
importance as selective therapeutic agents
