The shikimate pathway links metabolism of carbohydrates to biosynthesis of aromatic compounds. In a sequence of seven steps, phosphoenolpyruvate and erythrose 4-phosphate are converted to chorismate, a precursor of the aromatic amino acids and many secondary aromatic metabolites. The shikimate pathway is essential for most bacteria and plants but absent in humans, making it an attractive target for the development of novel antibiotics. The third step in the pathway consists of the dehydration of dehydroquinate to dehydroshikimate. This reaction can be catalyzed by two enzyme families which utilize distinct mechanisms. The protein structure presented here is representative of the type I enzyme family.
While previously reported type I dehydroquinate dehydratase structures have reliably displayed an open and/or disordered behavior in apo structures and an ordered and closed behavior in ligand bound structures, this structure displays the unusual property of a closed loop despite the absence of ligand. An examination of crystal packing reveals that an open conformation of the loop would clash with crystal contacts, implicating crystal packing in biasing the loop to a closed conformation. In this structure we find that a chloride atom from the crystallization solution is bound precisely where the substrate’s carboxylate is found in the ligand bound structures. This finding suggests that the protein has a general ability to coordinate anionic species to this position and provides a basis for previous reports of chloride acting as a competitive inhibitor type I dehydroquinate dehydration.