Disease relevance of C00944

• Dehydroquinate synthase, the enzyme which catalyzes the conversion of 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) to 5-dehydroquinate, has been purified from Bacillus subtilis in association with chorismate synthase and NADPH-dependent flavin reductase [1].
• The lysine residues involved in Schiff-base formation at the active sites of both the 3-dehydroquinase component of the pentafunctional arom enzyme of Neurospora crassa and of the monofunctional 3-dehydroquinase of Escherichia coli were labelled by treatment with 3-dehydroquinate in the presence of NaB3H4 [2].
• Structural study of the type II 3-dehydroquinate dehydratase from Actinobacillus pleuropneumoniae [3].
• The gene coding for the 3-dehydroquinate synthetase (aroB) of Neisseria gonorrhoeae has been cloned by functional complementation of an Escherichia coli aroB mutant [4].
• Sequence analysis revealed the evolution of DOI synthases from 3-dehydroquinate (DHQ) synthases in actinomycetes [5].

High impact information on C00944

• A possible five-step reaction mechanism is proposed for the cyclization reaction catalyzed by AcbC based on the recent analysis of the three-dimensional structure of a eukaryotic 3-dehydroquinate synthase domain (Carpenter, E. P., Hawkins, A. R., Frost, J. W., and Brown, K. A. (1998) Nature 394, 299-302) [6].
• Quinic acid formation results from the reduction of 3-dehydroquinic acid catalyzed by aroE-encoded shikimate dehydrogenase [7].
• Molecular characterization of tomato 3-dehydroquinate dehydratase-shikimate:NADP oxidoreductase [8].
• No orthologs are present in the genomes of the archaea encoding genes for the first two steps in the biosynthesis of the aromatic amino acids leading to 3-dehydroquinate (DHQ) [9].
• The AROM protein 3-dehydroquinase domain is sensitive to inactivation by borohydride in the presence of the substrate 3-dehydroquinate, confirming that it is a typical type I 3-dehydroquinase [10].

Chemical compound and disease context of C00944

• The conversion of 3-deoxy D-arabino heptulosonate 7-phosphate to 3-dehydroquinate by the 3-dehydroquinate synthetase from E. coli is characterized by a low but significant kinetic isotope effect for tritium carried in position-5 of DAHP, while no isotope effect was detectable for tritium in position-4 [11].
• Different glucose transport systems are examined for their impact on phosphoenolpyruvate availability as reflected by the yields of 3-dehydroshikimic acid and byproducts 3-deoxy-d-arabino-heptulosonic acid, 3-dehydroquinic acid, and gallic acid synthesized by Escherichia coli from glucose [12].

Biological context of C00944

• A 5.6-kb PstI fragment containing the structural gene (aroD) for 5-dehydroquinate hydrolyase (DHQase) of Escherichia coli K-12 has been cloned into recombinant plasmid pJKK12 [13].
• A 1.35 Md DNA HindIII fragment containing part of the arom gene cluster or cluster gene of Aspergillus nidulans encoding biosynthetic dehydroquinase (5-dehydroquinate hydrolyase) has been cloned in plasmid pBR322 on the basis of functional expression in Escherichia coli [14].
• The predicted amino acid sequence of the H. pylori aroB gene product showed significant homology (30-40% identity and 50-60% similarity) to 3-dehydroquinate synthases from various other prokaryotes and eukaryotes [15].
• The aroD gene from Salmonella typhi, encoding 5-dehydroquinate hydrolyase (3-dehydroquinase), has been cloned into Escherichia coli and the DNA sequence determined [16].

Anatomical context of C00944

• 3-Dehydroshikimate was formed with a yield of 57-77% from quinate via 3-dehydroquinate by two successive enzyme reactions, quinoprotein quinate dehydrogenase (QDH) and 3-dehydroquinate dehydratase, in the cytoplasmic membranes of acetic acid bacteria [17].

Associations of C00944 with other chemical compounds

• When quinate was incubated with the membrane fraction of acetic acid bacteria at pH 5.0, 3-dehydroquinate was formed as the predominant product [18].

Analytical, diagnostic and therapeutic context of C00944

• Crystallization of Aspergillus nidulans 3-dehydroquinate synthase (DHQS), following turnover of the enzyme by addition of the substrate DAHP, gave a new crystal form (form J) [19].

References