Gene Symbol: hldD
Description: ADP-L-glycero-D-mannoheptose-6-epimerase, NAD(P)-binding
Alias: ECK3609, JW3594, gmhD, htrM, nbsB, rfaD, waaD
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Missiakas D, Betton J, Raina S. New components of protein folding in extracytoplasmic compartments of Escherichia coli SurA, FkpA and Skp/OmpH. Mol Microbiol. 1996;21:871-84 pubmed
    ..Interestingly, surA was also selected as a multicopy suppressor of a defined htrM (rfaD) null mutation...
  2. Schnaitman C, Klena J. Genetics of lipopolysaccharide biosynthesis in enteric bacteria. Microbiol Rev. 1993;57:655-82 pubmed
  3. Pegues J, Chen L, Gordon A, Ding L, Coleman W. Cloning, expression, and characterization of the Escherichia coli K-12 rfaD gene. J Bacteriol. 1990;172:4652-60 pubmed
    The rfaD gene encodes ADP-L-glycero-D-mannoheptose-6-epimerase, an enzyme required for the biosynthesis of the lipopolysaccharide precursor ADP-L-glycerol-D-mannoheptose. The precise localization of the rfaD gene on a 1...
  4. Joloba M, Clemmer K, Sledjeski D, Rather P. Activation of the gab operon in an RpoS-dependent manner by mutations that truncate the inner core of lipopolysaccharide in Escherichia coli. J Bacteriol. 2004;186:8542-6 pubmed
    ..A Tn5tmp insertion in the hldD (formerly rfaD) gene increased gabT::lacZ expression 12-fold...
  5. Morrison J, Tanner M. A two-base mechanism for Escherichia coli ADP-L-glycero-D-manno-heptose 6-epimerase. Biochemistry. 2007;46:3916-24 pubmed
    ADP-l-glycero-d-manno-heptose 6-epimerase (HldD or AGME, formerly RfaD) catalyzes the inversion of configuration at C-6' ' of the heptose moiety of ADP-d-glycero-d-manno-heptose and ADP-l-glycero-d-manno-heptose...
  6. Ding L, Seto B, Ahmed S, Coleman W. Purification and properties of the Escherichia coli K-12 NAD-dependent nucleotide diphosphosugar epimerase, ADP-L-glycero-D-mannoheptose 6-epimerase. J Biol Chem. 1994;269:24384-90 pubmed
    ..The native enzyme displays UV and fluorescence spectra that are consistent with the presence of enzyme bound NAD+. CD spectra of the holoepimerase indicate 11% alpha-helical and 36% beta-sheet structures. ..
  7. Coleman W. The rfaD gene codes for ADP-L-glycero-D-mannoheptose-6-epimerase. An enzyme required for lipopolysaccharide core biosynthesis. J Biol Chem. 1983;258:1985-90 pubmed
    The rfaD gene product, ADP-L-glycero-D-mannoheptose-6-epimerase, is necessary for the conversion of ADP-D-glycero-D-mannoheptose to ADP-L-glycero-D-mannoheptose...
  8. Coleman W, Deshpande K. New cysE-pyrE-linked rfa mutation in Escherichia coli K-12 that results in a heptoseless lipopolysaccharide. J Bacteriol. 1985;161:1209-14 pubmed
    ..Plasmids carrying the wild-type rfaD70+ allele failed to abolish the rfa-2 phenotypes. Further, the rfaD gene product, ADP-L-glycero-D-mannoheptose-6-epimerase, was detected in crude extracts of a rfa-2 mutant strain, ..
  9. Schnaitman C, Parker C, Klena J, Pradel E, Pearson N, Sanderson K, et al. Physical maps of the rfa loci of Escherichia coli K-12 and Salmonella typhimurium. J Bacteriol. 1991;173:7410-1 pubmed

More Information


  1. Raina S, Georgopoulos C. The htrM gene, whose product is essential for Escherichia coli viability only at elevated temperatures, is identical to the rfaD gene. Nucleic Acids Res. 1991;19:3811-9 pubmed
    ..Surprisingly, the htrM gene turns out to be identical to rfaD, whose product is required for the biosynthesis of the ADP-L-glycero-D manoheptose lipopolyaccharide precursor [..
  2. Klena J, Pradel E, Schnaitman C. Comparison of lipopolysaccharide biosynthesis genes rfaK, rfaL, rfaY, and rfaZ of Escherichia coli K-12 and Salmonella typhimurium. J Bacteriol. 1992;174:4746-52 pubmed
    ..coli K-12 and S. typhimurium, as do the rfaF and rfaD genes which lie beyond it...
  3. Coleman W, Leive L. Two mutations which affect the barrier function of the Escherichia coli K-12 outer membrane. J Bacteriol. 1979;139:899-910 pubmed
    ..The order of the genes in this region, based on transductional analyses, is proC NbsA plsA purE. The second, NbsB, lies at 80 min. The order of the genes in this region, based on transduction analyses, is xyl cysE NbsB pyrE...
  4. Deacon A, Ni Y, Coleman W, Ealick S. The crystal structure of ADP-L-glycero-D-mannoheptose 6-epimerase: catalysis with a twist. Structure. 2000;8:453-62 pubmed
    ..This study should prove useful in the design of mechanistic and structure-based inhibitors of the AGME catalyzed reaction. ..
  5. Ni Y, McPhie P, Deacon A, Ealick S, Coleman W. Evidence that NADP+ is the physiological cofactor of ADP-L-glycero-D-mannoheptose 6-epimerase. J Biol Chem. 2001;276:27329-34 pubmed
    ..A structural comparison of ADP-hep 6-epimerase with UDP-galactose 4-epimerase, which utilizes an NAD(+) cofactor, has identified the regions of ADP-hep 6-epimerase, which defines its specificity for NADP(+). ..
  6. Morrison J, Read J, Coleman W, Tanner M. Dismutase activity of ADP-L-glycero-D-manno-heptose 6-epimerase: evidence for a direct oxidation/reduction mechanism. Biochemistry. 2005;44:5907-15 pubmed
    ..The epimerase (HldD or AGME, formerly RfaD) operates in the biosynthetic pathway of l-glycero-d-manno-heptose, which is a conserved ..
  7. Reyes Cortes R, Martínez Peñafiel E, Martínez Pérez F, de la Garza M, Kameyama L. A novel strategy to isolate cell-envelope mutants resistant to phage infection: bacteriophage mEp213 requires lipopolysaccharides in addition to FhuA to enter Escherichia coli K-12. Microbiology. 2012;158:3063-71 pubmed publisher
    ..that we selected, six were in the fhuA gene, two were mutated in the waaC gene, and one was mutated in the gmhD gene. The latter two gene products are involved in the synthesis of lipopolysaccharide (LPS)...
  8. Mayer A, Tanner M. Intermediate release by ADP-L-glycero-D-manno-heptose 6-epimerase. Biochemistry. 2007;46:6149-55 pubmed
    ADP-l-glycero-d-manno-heptose 6-epimerase (HldD or AGME, formerly RfaD) catalyzes the interconversion of ADP-beta-d-glycero-d-manno-heptose (ADP-d,d-Hep) and ADP-beta-l-glycero-d-manno-heptose (ADP-l,d-Hep)...
  9. Roncero C, Casadaban M. Genetic analysis of the genes involved in synthesis of the lipopolysaccharide core in Escherichia coli K-12: three operons in the rfa locus. J Bacteriol. 1992;174:3250-60 pubmed
    ..The genetic organization of this locus seems to be identical in E. coli K-12 and S. typhimurium. ..
  10. Read J, Ahmed R, Morrison J, Coleman W, Tanner M. The mechanism of the reaction catalyzed by ADP-beta-L-glycero-D-manno-heptose 6-epimerase. J Am Chem Soc. 2004;126:8878-9 pubmed
    ADP-l-glycero-d-manno-heptose 6-epimerase (AGME, RfaD) is a bacterial enzyme that is involved in lipopolysaccharide biosynthesis and interconverts ADP-beta-l-glycero-d-manno-heptose (ADP-l,d-Hep) with ADP-beta-d-glycero-d-manno-heptose (..
  11. Kneidinger B, Marolda C, Graninger M, Zamyatina A, McArthur F, Kosma P, et al. Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli. J Bacteriol. 2002;184:363-9 pubmed
    ..A previously characterized epimerase, formerly named WaaD (RfaD) and now renamed HldD, completes the pathway to form the ADP-L-beta-D-heptose precursor utilized in the assembly of inner core LPS.
  12. Sirisena D, MacLachlan P, Liu S, Hessel A, Sanderson K. Molecular analysis of the rfaD gene, for heptose synthesis, and the rfaF gene, for heptose transfer, in lipopolysaccharide synthesis in Salmonella typhimurium. J Bacteriol. 1994;176:2379-85 pubmed
    ..typhimurium LT2 which we identified as rfaF, the structural gene for ADP-heptose:LPS heptosyltransferase II; rfaD, the structural gene for ADP-L-glycero-D-manno-heptose-6-epimerase; and part of kbl, the structural gene for 2-..
  13. Holland A, Rather P. Evidence for extracellular control of RpoS proteolysis in Escherichia coli. FEMS Microbiol Lett. 2008;286:50-9 pubmed publisher
    ..However, protease treatment drastically reduced signal activity. Extracellular signal activity was absent in an hldD (rfaD) mutant, but was present in cell lysates, suggesting that signal was unable to be exported in an hldD mutant.
  14. Karow M, Raina S, Georgopoulos C, Fayet O. Complex phenotypes of null mutations in the htr genes, whose products are essential for Escherichia coli growth at elevated temperatures. Res Microbiol. 1991;142:289-94 pubmed
    ..The htrM gene is identical to the rfaD gene, whose product is required for the biosynthesis of the lipopolysaccharide precursor ADP-L-glycero-D-..