Structure and Function of Enzymes of Shikimate Pathway
The shikimate pathway is found in microorganisms, fungi, plants and also in several apicomplexan parasites.
This metabolic pathway consists of seven enzymes and converts the primary metabolites phosphoenolpyruvate and
erythrose-4-phosphate to chorismate, the last common precursor for the three aromatic amino acids Phe, Tyr, and Trp and
other aromatic compounds. The significance of targeting the enzymes of this pathway as selective targets for anti
microbial drug design involves the fact that they are essential for microbes but absent in humans.
In present scenario, the emergence of multi-drug resistance in pathogenic bacteria and herbicide resistance in weeds is of
great clinical and agro-economical concern. Therefore in this review, we did the comparative sequence and threedimensional
structure analysis of these enzymes from various microorganisms and plants for structure-function analysis,
motif search, common structural signatures of active site and elucidation of regulation mechanisms. Also, the available
structures of five shikimate pathway enzymes from M. tuberculosis, a dreadful microorganism, which causes 1.5 million
deaths per year, have been comparatively analyzed with other reported homologous structures. To get the structural
insight of remaining two shikimate pathway enzymes (dehydroquinate synthase and shikimate-5-dehydrogenase) of M.
tuberculosis we did molecular modeling to find out key active site residues. These studies can further be proven helpful in
designing novel structure based antimicrobial drugs.
Keywords: Aromatic amino acid, crystal structure, enzyme, homology model, mycobacterium tuberculosis, shikimate pathway, antimicrobial drugs, Salmonella enterica, Aquifex aeolicus, Clostridium difficile
Rights & PermissionsPrintExport