Current Bioinformatics

Yi-Ping Phoebe Chen
Department of Computer Science and Information Technology
La Trobe University
Melbourne
Australia

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Structure and Function of Enzymes of Shikimate Pathway

Author(s): Aditya Dev, Satya Tapas, Shivendra Pratap, Pravindra Kumar.

Abstract:

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

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Article Details

VOLUME: 7
ISSUE: 4
Year: 2012
Page: [374 - 391]
Pages: 18
DOI: 10.2174/157489312803900983
Price: $58