Disease relevance of dTDP-D-glucose

• The stereochemical course of the dTDP-glucose oxidoreductase (EC 4.2.1.46) reaction was studied using enzyme partially purified from Escherichia coli and dTDP-(6R)- and (6S)-[4-2H, 6-3H]glucose as substrate [1].
• High resolution X-ray structure of dTDP-glucose 4,6-dehydratase from Streptomyces venezuelae [2].
• The dTDP-glucose 4,6-dehydratase catalyzed conversion of dTDP-glucose to dTDP-4-keto-6-deoxyglucose occurs in three sequential chemical steps: dehydrogenation, dehydration, and rereduction [3].
• Drug targeting Mycobacterium tuberculosis cell wall synthesis: genetics of dTDP-rhamnose synthetic enzymes and development of a microtiter plate-based screen for inhibitors of conversion of dTDP-glucose to dTDP-rhamnose [4].

High impact information on dTDP-D-glucose

• The enzyme catalyses the formation of dTDP-glucose, from dTTP and glucose 1-phosphate, as well as its pyrophosphorolysis [5].
• The conversion of dTDP-glucose into dTDP-4-keto-6-deoxyglucose by Escherichia coli dTDP-glucose 4,6-dehydratase (4,6-dehydratase) takes place in the active site in three steps: dehydrogenation to dTDP-4-ketoglucose, dehydration to dTDP-4-ketoglucose-5,6-ene, and rereduction of C6 to the methyl group [6].
• Escherichia coli dTDP-glucose 4,6-dehydratase and UDP-galactose 4-epimerase are members of the short-chain dehydrogenase/reductase SDR family [7].
• Based on amino acid sequence homology, LPS sugar composition, and enzymatic activity, we concluded that lpsbeta2 codes for an enzyme involved in the transformation of dTDP-glucose into dTDP-rhamnose, the sugar donor of rhamnose for the synthesis of O-antigen [8].
• Two inserts had similarity to arsenic-resistance genes, whereas four others had similarities to cytochrome c oxidase III, dTDP-glucose 4,6-dehydratase, gamma-glutamyl transpeptidase and an abortive phage-resistance protein [9].

Chemical compound and disease context of dTDP-D-glucose

• An Escherichia coli rmIC mutant was constructed and a crude enzyme extract prepared from it did not produce dTDP-4-keto-rhamnose, in contrast to a crude enzyme extract prepared from a wild-type E. coli strain where small amounts of this intermediate were found after incubation with dTDP-glucose in the absence of NADPH [10].

Biological context of dTDP-D-glucose

• The deduced amino acid sequence of AviE, encoded by ORF4, shows 55% identity to a dTDP-glucose dehydratase (StrE) from S. griseus [11].
• Genes for dTDP-glucose synthase and dehydratase occur in other gene clusters for antibiotic production [12].
• Cultures of Escherichia coli containing plasmids with ORF2, on a 2.1 kb BamHI fragment, were able to catalyze the formation of dTDP-4-keto-6-deoxy-D-glucose from dTDP-glucose at 5 times the rate of control cultures, confirming that ORF2 encodes a dTDP-glucose dehydratase [13].
• The enzyme showed substrate specificity only to dTDP-glucose [14].
• By DNA sequence analysis, seven amplified fragments showed high homology with dTDP-glucose synthase genes that participate in the biosynthesis of secondary metabolites or in deoxy-sugar moieties in lipopolysaccharides [14].

Associations of dTDP-D-glucose with other chemical compounds

• We demonstrated that one of these ORFs, blmA, confers resistance against the antibiotic dihydrostreptomycin, and another, blmD, encodes a dTDP-glucose synthase [15].

Gene context of dTDP-D-glucose

• The amino acid sequence encoded by ORF3 (GraD) is 51.4% identical (69.9% similar) to that of StrD, a dTDP-glucose synthase from Streptomyces griseus [13].
• In addition, we have cloned a 45-kb region of DNA from Streptomyces spectabilis ATCC27741, a spectinomycin producer which contained the dTDP-glucose synthase and dTDP-glucose 4,6-dehydratase genes named spcD and spcE, respectively [14].

Analytical, diagnostic and therapeutic context of dTDP-D-glucose

• Specifically designed PCR primers were applied to amplify a segment of dTDP-glucose synthase gene from six actinomycete strains [14].

References