Crystal structure of type I 3-dehydroquinate dehydratase of Aquifex aeolicus suggests closing of active site flap is not essential for enzyme action

Abstract

Structural analyses of enzymes involved in biosynthetic pathways that are present in micro-organisms, but absent from mammals (for example Shikimate pathway) are important in developing anti-microbial drugs. Crystal structure of the Shikimate pathway enzyme, type I 3-dehydroquinate dehydratase (3-DHQase) from the hyperthermophilic bacterium Aquifex aeolicus was solved both as an apo form and in complex with a ligand. The complex structure revealed an interesting structural difference when compared to other ligand-bound type I 3-DHQases suggesting that closure of the active site loop is not essential for catalysis. This provides new insights into the catalytic mechanism of type I 3-DHQases.