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Gene Review

gnd  -  6-phosphogluconate dehydrogenase

Escherichia coli O157:H7 str. EDL933

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Disease relevance of gnd

  • In contrast, recombination at gnd has occurred with such high frequency in Escherichia coli that the indicated evolutionary relationships among strains are not congruent with those estimated by sequence analysis of other genes and by multilocus enzyme electrophoresis [1].
  • The relatively frequent exchange of gnd within and among taxonomic groups of the Enterobacteriaceae, compared with other housekeeping genes, apparently results from its close linkage with genes that are subject to diversifying selection, including those of the rfb region determining the structure of the O antigen polysaccharide [1].
  • E. coli and S. enterica apparently have not exchanged gnd sequences, but those of several strains of E. coli have been imported from species of Citrobacter and Klebsiella [1].
  • Molecular evolution in the gnd locus of Salmonella enterica [2].
  • One terminus of this translocatable segment was near gnd and was the same as a terminus of the his-gnd segment of the phage which translocated from the chromosome of the nonlysogenic transductant [3].

High impact information on gnd

  • Previous results obtained with strains carrying transcriptional fusions of gnd to the structural genes of the lactose operon suggested that the growth rate-dependent regulation of gnd expression is at the post-transcriptional level [4].
  • Six gnd alleles coding for naturally occurring allozymes of 6-phosphogluconate dehydrogenase [6-phospho-D-gluconate:NAD(P)+ 2-oxidoreductase, EC] have been transferred by transduction into the genetic background of Escherichia coli K-12 and examined for their selective effects in chemostats in which gluconate was limiting [5].
  • Enzymes from the pentose phosphate pathway (PPP) are potential drug targets for the development of new drugs against Trypanosoma brucei, the causative agent of African sleeping disease: for instance, the 6-phosphogluconate dehydrogenase is currently studied actively for such purposes [6].
  • As previously reported, the incongruence observed between the gnd and plasmid gene data and the whole-genome data was multiple, indicating numerous horizontal transfer and/or recombination events [7].
  • Comparison of the two O86 O-antigen gene clusters revealed that the encoding regions between galF and gnd are identical, including wzy genes [8].

Chemical compound and disease context of gnd

  • To determine whether growth rate-dependent regulation of expression of gnd, which encodes this enzyme, is carried out by a transcriptional mechanism, the structural genes of the lactose operon were fused to and brought under the control of the gnd promoter through the use of phage Mu d1(Apr lac) [9].

Biological context of gnd

  • The E. coli O145 gene cluster is located between the JUMPStart sequence and the gnd gene and consists of 15 open reading frames [10].
  • Models for regulation are discussed with respect to these results and the physiology and DNA sequence of gnd [9].
  • Characteristically, all genes specific to O-antigen synthesis are clustered in a region close to the his and gnd genes on the chromosome of Escherichia coli and related species [11].
  • Previous work with gnd-lac operon and protein fusion strains indicated that two steps in the expression of the gnd gene are subject to growth rate-dependent control, with at least one step being posttranscriptional [12].
  • Inhibition of translation initiation on Escherichia coli gnd mRNA by formation of a long-range secondary structure involving the ribosome binding site and the internal complementary sequence [13].

Anatomical context of gnd

  • Taken together, these data support the hypothesis that the role of the ICS in the growth rate-dependent regulation of gnd expression is to sequester the translation initiation region into a long-range mRNA secondary structure that blocks ribosome binding and thereby reduces the frequency of translation initiation [13].

Associations of gnd with chemical compounds

  • With both Northern (RNA) and slot blot analyses, we found that the amount of gnd mRNA relative to that of total RNA was 2.5-fold higher in cells growing in glucose minimal medium than in cells grown on acetate [12].
  • Neither ppGpp nor pppGpp appeared to influence gnd gene expression [14].
  • Finally, RNA structure mapping experiments indicated that the presence of the ICS in gnd mRNA reduces the access of the nucleotides of the ribosome binding site to the single-strand-specific chemical reagents dimethyl sulfate and kethoxal [13].
  • Over-generated NADPH by the amplified gnd gene tended to depress the cell growth and PHB concentration [15].

Other interactions of gnd

  • The O-antigen gene cluster of E. coli O52, which is located between the galF and gnd genes, was found to contain putative genes for the synthesis of the O-antigen constituents, sugar transferase genes, and ABC-2 transporter genes [16].
  • The his-nif plasmids pRD1 and pTM4010 contain the genes gnd rfb his nif shiA [17].

Analytical, diagnostic and therapeutic context of gnd


  1. Intergeneric transfer and recombination of the 6-phosphogluconate dehydrogenase gene (gnd) in enteric bacteria. Nelson, K., Selander, R.K. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  2. Molecular evolution in the gnd locus of Salmonella enterica. Thampapillai, G., Lan, R., Reeves, P.R. Mol. Biol. Evol. (1994) [Pubmed]
  3. Integration of specialized transducing bacteriophage lambda cI857 St68 h80 dgnd his by an unusual pathway promotes formation of deletions and generates a new translocatable element. Wolf, R.E. J. Bacteriol. (1980) [Pubmed]
  4. Essential site for growth rate-dependent regulation within the Escherichia coli gnd structural gene. Baker, H.V., Wolf, R.E. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  5. Potential for selection among nearly neutral allozymes of 6-phosphogluconate dehydrogenase in Escherichia coli. Hartl, D.L., Dykhuizen, D.E. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  6. Three Dimensional Structure and Implications for the Catalytic Mechanism of 6-Phosphogluconolactonase from Trypanosoma brucei. Delarue, M., Duclert-Savatier, N., Miclet, E., Haouz, A., Giganti, D., Ouazzani, J., Lopez, P., Nilges, M., Stoven, V. J. Mol. Biol. (2007) [Pubmed]
  7. Escherichia coli molecular phylogeny using the incongruence length difference test. Lecointre, G., Rachdi, L., Darlu, P., Denamur, E. Mol. Biol. Evol. (1998) [Pubmed]
  8. Molecular analysis of the O-antigen gene cluster of Escherichia coli O86:B7 and characterization of the chain length determinant gene (wzz). Guo, H., Yi, W., Shao, J., Lu, Y., Zhang, W., Song, J., Wang, P.G. Appl. Environ. Microbiol. (2005) [Pubmed]
  9. Growth rate-dependent regulation of 6-phosphogluconate dehydrogenase level in Escherichia coli K-12: beta-galactosidase expression in gnd-lac operon fusion strains. Baker, H.V., Wolf, R.E. J. Bacteriol. (1983) [Pubmed]
  10. Structural and genetic characterization of enterohemorrhagic Escherichia coli O145 O antigen and development of an O145 serogroup-specific PCR assay. Feng, L., Senchenkova, S.N., Tao, J., Shashkov, A.S., Liu, B., Shevelev, S.D., Reeves, P.R., Xu, J., Knirel, Y.A., Wang, L. J. Bacteriol. (2005) [Pubmed]
  11. Escherichia coli clone Sonnei (Shigella sonnei) had a chromosomal O-antigen gene cluster prior to gaining its current plasmid-borne O-antigen genes. Lai, V., Wang, L., Reeves, P.R. J. Bacteriol. (1998) [Pubmed]
  12. Determination of the growth rate-regulated steps in expression of the Escherichia coli K-12 gnd gene. Pease, A.J., Wolf, R.E. J. Bacteriol. (1994) [Pubmed]
  13. Inhibition of translation initiation on Escherichia coli gnd mRNA by formation of a long-range secondary structure involving the ribosome binding site and the internal complementary sequence. Chang, J.T., Green, C.B., Wolf, R.E. J. Bacteriol. (1995) [Pubmed]
  14. Mutation spoT of Escherichia coli increases expression of the histidine operon deleted for the attenuator. Winkler, M.E., Zawodny, R.V., Hartman, P.E. J. Bacteriol. (1979) [Pubmed]
  15. Metabolic engineering of pentose phosphate pathway in Ralstoniaeutropha for enhanced biosynthesis of poly-beta-hydroxybutyrate. Lee, J.N., Shin, H.D., Lee, Y.H. Biotechnol. Prog. (2003) [Pubmed]
  16. Synthesis of the heteropolysaccharide O antigen of Escherichia coli O52 requires an ABC transporter: structural and genetic evidence. Feng, L., Senchenkova, S.N., Yang, J., Shashkov, A.S., Tao, J., Guo, H., Cheng, J., Ren, Y., Knirel, Y.A., Reeves, P.R., Wang, L. J. Bacteriol. (2004) [Pubmed]
  17. Order of genes near nif in Klebsiella pneumoniae. MacNeil, D., Supiano, M.A., Brill, W.J. J. Bacteriol. (1979) [Pubmed]
  18. Characterization of Escherichia coli O86 O-antigen gene cluster and identification of O86-specific genes. Feng, L., Han, W., Wang, Q., Bastin, D.A., Wang, L. Vet. Microbiol. (2005) [Pubmed]
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