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Title
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The two types of 3-dehydroquinase have distinct structures but catalyze the same overall reaction.
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Authors
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D.G.Gourley,
A.K.Shrive,
I.Polikarpov,
T.Krell,
J.R.Coggins,
A.R.Hawkins,
N.W.Isaacs,
L.Sawyer.
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Ref.
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Nat Struct Biol, 1999,
6,
521-525.
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PubMed id
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Abstract
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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.
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