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Protein

ADP-L-glycero-D-manno-heptose-6-epimerase

Gene

hldD

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the interconversion between ADP-D-glycero-beta-D-manno-heptose and ADP-L-glycero-beta-D-manno-heptose via an epimerization at carbon 6 of the heptose.2 Publications

Catalytic activityi

ADP-D-glycero-D-manno-heptose = ADP-L-glycero-D-manno-heptose.1 Publication

Cofactori

NADP+2 Publications, NAD+2 PublicationsNote: Binds 1 NADP+ per subunit. NAD+ can substitute for NADP+, but enzymatic activity is reduced.2 Publications

Enzyme regulationi

Completely inhibited by ADP and ADP-glucose, and partially inhibited by ATP and NADH.

Kineticsi

  1. KM=0.1 mM for ADP-heptose1 Publication
  1. Vmax=1.53 µmol/min/mg enzyme1 Publication

pH dependencei

Optimum pH is 5.5-9.5.1 Publication

Temperature dependencei

Optimum temperature is 42 degrees Celsius.1 Publication

Pathwayi: ADP-L-glycero-beta-D-manno-heptose biosynthesis

This protein is involved in step 4 of the subpathway that synthesizes ADP-L-glycero-beta-D-manno-heptose from D-glycero-beta-D-manno-heptose 7-phosphate.
Proteins known to be involved in the 4 steps of the subpathway in this organism are:
  1. Bifunctional protein HldE (hldE)
  2. D-glycero-beta-D-manno-heptose-1,7-bisphosphate 7-phosphatase (gmhB)
  3. Bifunctional protein HldE (hldE)
  4. ADP-L-glycero-D-manno-heptose-6-epimerase (hldD)
This subpathway is part of the pathway ADP-L-glycero-beta-D-manno-heptose biosynthesis, which is itself part of Nucleotide-sugar biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes ADP-L-glycero-beta-D-manno-heptose from D-glycero-beta-D-manno-heptose 7-phosphate, the pathway ADP-L-glycero-beta-D-manno-heptose biosynthesis and in Nucleotide-sugar biosynthesis.

Pathwayi: LPS core biosynthesis

This protein is involved in the pathway LPS core biosynthesis, which is part of Bacterial outer membrane biogenesis.
View all proteins of this organism that are known to be involved in the pathway LPS core biosynthesis and in Bacterial outer membrane biogenesis.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei38 – 381NADP1 Publication
Binding sitei53 – 531NADP1 Publication
Binding sitei92 – 921NADP1 Publication
Active sitei140 – 1401Proton acceptor1 Publication
Binding sitei144 – 1441NADP1 Publication
Binding sitei169 – 1691Substrate1 Publication
Binding sitei170 – 1701NADP; via amide nitrogen1 Publication
Active sitei178 – 1781Proton acceptor1 Publication
Binding sitei178 – 1781NADP1 Publication
Binding sitei180 – 1801Substrate; via carbonyl oxygen1 Publication
Binding sitei187 – 1871Substrate1 Publication
Binding sitei209 – 2091Substrate1 Publication
Binding sitei272 – 2721Substrate1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi10 – 112NADP1 Publication
Nucleotide bindingi31 – 322NADP1 Publication
Nucleotide bindingi75 – 795NADP1 Publication

GO - Molecular functioni

  • ADP-glyceromanno-heptose 6-epimerase activity Source: EcoCyc
  • NADP+ binding Source: EcoCyc

GO - Biological processi

  • ADP-L-glycero-beta-D-manno-heptose biosynthetic process Source: UniProtKB-UniPathway
  • lipopolysaccharide core region biosynthetic process Source: EcoCyc
Complete GO annotation...

Keywords - Molecular functioni

Isomerase

Keywords - Biological processi

Carbohydrate metabolism, Lipopolysaccharide biosynthesis, Stress response

Keywords - Ligandi

NAD, NADP

Enzyme and pathway databases

BioCyciEcoCyc:EG10838-MONOMER.
ECOL316407:JW3594-MONOMER.
MetaCyc:EG10838-MONOMER.
BRENDAi5.1.3.20. 2026.
SABIO-RKP67910.
UniPathwayiUPA00356; UER00440.
UPA00958.

Names & Taxonomyi

Protein namesi
Recommended name:
ADP-L-glycero-D-manno-heptose-6-epimerase (EC:5.1.3.201 Publication)
Alternative name(s):
ADP-L-glycero-beta-D-manno-heptose-6-epimerase
Short name:
ADP-glyceromanno-heptose 6-epimerase
Short name:
ADP-hep 6-epimerase
Short name:
AGME
Gene namesi
Name:hldD
Synonyms:htrM, rfaD, waaD
Ordered Locus Names:b3619, JW3594
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG10838. hldD.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • membrane Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi140 – 1401Y → F: Severely compromises epimerase activitie. 1 Publication
Mutagenesisi178 – 1781K → M: Severely compromises epimerase activitie. 1 Publication
Mutagenesisi208 – 2081K → M: Activity similar to that of the wild-type. 1 Publication
Mutagenesisi210 – 2101D → N: Activity similar to that of the wild-type. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 310310ADP-L-glycero-D-manno-heptose-6-epimerasePRO_0000205793Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei267 – 2671N6-acetyllysine1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP67910.
PaxDbiP67910.
PRIDEiP67910.

2D gel databases

SWISS-2DPAGEP67910.

Expressioni

Inductioni

By heat shock.

Interactioni

Subunit structurei

Homopentamer.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
menBP0ABU02EBI-543760,EBI-554195

Protein-protein interaction databases

BioGridi4263293. 559 interactions.
DIPiDIP-35958N.
IntActiP67910. 39 interactions.
STRINGi511145.b3619.

Structurei

Secondary structure

1
310
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi2 – 54Combined sources
Turni6 – 83Combined sources
Helixi10 – 2011Combined sources
Turni21 – 233Combined sources
Beta strandi27 – 315Combined sources
Helixi36 – 394Combined sources
Helixi40 – 434Combined sources
Beta strandi48 – 525Combined sources
Helixi53 – 619Combined sources
Beta strandi71 – 744Combined sources
Helixi86 – 927Combined sources
Helixi94 – 10714Combined sources
Beta strandi111 – 1166Combined sources
Helixi117 – 1204Combined sources
Helixi131 – 1333Combined sources
Helixi139 – 15416Combined sources
Helixi155 – 1573Combined sources
Beta strandi162 – 1676Combined sources
Beta strandi169 – 1746Combined sources
Helixi176 – 1816Combined sources
Helixi184 – 19310Combined sources
Beta strandi199 – 2035Combined sources
Helixi204 – 2063Combined sources
Beta strandi211 – 2133Combined sources
Helixi214 – 22714Combined sources
Beta strandi231 – 2366Combined sources
Helixi243 – 2497Combined sources
Helixi251 – 2544Combined sources
Beta strandi260 – 2623Combined sources
Helixi266 – 2683Combined sources
Turni269 – 2713Combined sources
Helixi281 – 2855Combined sources
Helixi295 – 30511Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1EQ2X-ray2.00A/B/C/D/E/F/G/H/I/J1-310[»]
2X6TX-ray2.36A/B/C/D/E/F/G/H/I/J1-310[»]
ProteinModelPortaliP67910.
SMRiP67910. Positions 1-308.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP67910.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni201 – 2044Substrate binding1 Publication

Domaini

Contains a large N-terminal NADP-binding domain associated with a modified Rossman fold, and a smaller C-terminal substrate-binding domain.

Sequence similaritiesi

Phylogenomic databases

eggNOGiENOG4105CUI. Bacteria.
COG0451. LUCA.
HOGENOMiHOG000167987.
InParanoidiP67910.
KOiK03274.
OMAiKGRYQSF.
OrthoDBiEOG6384GP.
PhylomeDBiP67910.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
HAMAPiMF_01601. Heptose_epimerase.
InterProiIPR001509. Epimerase_deHydtase_N.
IPR011912. Heptose_epim.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF01370. Epimerase. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.
TIGRFAMsiTIGR02197. heptose_epim. 1 hit.

Sequencei

Sequence statusi: Complete.

P67910-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIIVTGGAGF IGSNIVKALN DKGITDILVV DNLKDGTKFV NLVDLNIADY
60 70 80 90 100
MDKEDFLIQI MAGEEFGDVE AIFHEGACSS TTEWDGKYMM DNNYQYSKEL
110 120 130 140 150
LHYCLEREIP FLYASSAATY GGRTSDFIES REYEKPLNVY GYSKFLFDEY
160 170 180 190 200
VRQILPEANS QIVGFRYFNV YGPREGHKGS MASVAFHLNT QLNNGESPKL
210 220 230 240 250
FEGSENFKRD FVYVGDVADV NLWFLENGVS GIFNLGTGRA ESFQAVADAT
260 270 280 290 300
LAYHKKGQIE YIPFPDKLKG RYQAFTQADL TNLRAAGYDK PFKTVAEGVT
310
EYMAWLNRDA
Length:310
Mass (Da):34,893
Last modified:October 11, 2004 - v1
Checksum:i4B9388A879CB7522
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M33577 Genomic DNA. Translation: AAA24525.1.
X54492 Genomic DNA. Translation: CAA38364.1.
U00039 Genomic DNA. Translation: AAB18596.1.
U00096 Genomic DNA. Translation: AAC76643.1.
AP009048 Genomic DNA. Translation: BAE77673.1.
PIRiJU0299.
RefSeqiNP_418076.1. NC_000913.3.
WP_000587764.1. NZ_LN832404.1.

Genome annotation databases

EnsemblBacteriaiAAC76643; AAC76643; b3619.
BAE77673; BAE77673; BAE77673.
GeneIDi948134.
KEGGiecj:JW3594.
eco:b3619.
PATRICi32122725. VBIEscCol129921_3739.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M33577 Genomic DNA. Translation: AAA24525.1.
X54492 Genomic DNA. Translation: CAA38364.1.
U00039 Genomic DNA. Translation: AAB18596.1.
U00096 Genomic DNA. Translation: AAC76643.1.
AP009048 Genomic DNA. Translation: BAE77673.1.
PIRiJU0299.
RefSeqiNP_418076.1. NC_000913.3.
WP_000587764.1. NZ_LN832404.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1EQ2X-ray2.00A/B/C/D/E/F/G/H/I/J1-310[»]
2X6TX-ray2.36A/B/C/D/E/F/G/H/I/J1-310[»]
ProteinModelPortaliP67910.
SMRiP67910. Positions 1-308.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4263293. 559 interactions.
DIPiDIP-35958N.
IntActiP67910. 39 interactions.
STRINGi511145.b3619.

2D gel databases

SWISS-2DPAGEP67910.

Proteomic databases

EPDiP67910.
PaxDbiP67910.
PRIDEiP67910.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC76643; AAC76643; b3619.
BAE77673; BAE77673; BAE77673.
GeneIDi948134.
KEGGiecj:JW3594.
eco:b3619.
PATRICi32122725. VBIEscCol129921_3739.

Organism-specific databases

EchoBASEiEB0831.
EcoGeneiEG10838. hldD.

Phylogenomic databases

eggNOGiENOG4105CUI. Bacteria.
COG0451. LUCA.
HOGENOMiHOG000167987.
InParanoidiP67910.
KOiK03274.
OMAiKGRYQSF.
OrthoDBiEOG6384GP.
PhylomeDBiP67910.

Enzyme and pathway databases

UniPathwayiUPA00356; UER00440.
UPA00958.
BioCyciEcoCyc:EG10838-MONOMER.
ECOL316407:JW3594-MONOMER.
MetaCyc:EG10838-MONOMER.
BRENDAi5.1.3.20. 2026.
SABIO-RKP67910.

Miscellaneous databases

EvolutionaryTraceiP67910.
PROiP67910.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
HAMAPiMF_01601. Heptose_epimerase.
InterProiIPR001509. Epimerase_deHydtase_N.
IPR011912. Heptose_epim.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF01370. Epimerase. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.
TIGRFAMsiTIGR02197. heptose_epim. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning, expression, and characterization of the Escherichia coli K-12 rfaD gene."
    Pegues J.C., Chen L., Gordon A.W., Ding L., Coleman W.G. Jr.
    J. Bacteriol. 172:4652-4660(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-34.
    Strain: K12.
  2. "The htrM gene, whose product is essential for Escherichia coli viability only at elevated temperatures, is identical to the rfaD gene."
    Raina S., Georgopoulos C.
    Nucleic Acids Res. 19:3811-3819(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: K12.
  3. "Analysis of the Escherichia coli genome. V. DNA sequence of the region from 76.0 to 81.5 minutes."
    Sofia H.J., Burland V., Daniels D.L., Plunkett G. III, Blattner F.R.
    Nucleic Acids Res. 22:2576-2586(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / MG1655 / ATCC 47076.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / MG1655 / ATCC 47076.
  5. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
    Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
    Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  6. "Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12."
    Link A.J., Robison K., Church G.M.
    Electrophoresis 18:1259-1313(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 1-12.
    Strain: K12 / EMG2.
  7. Frutiger S., Hughes G.J., Pasquali C., Hochstrasser D.F.
    Submitted (FEB-1996) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 1-11.
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  8. "Purification and properties of the Escherichia coli K-12 NAD-dependent nucleotide diphosphosugar epimerase, ADP-L-glycero-D-mannoheptose 6-epimerase."
    Ding L., Seto B.L., Ahmed S.A., Coleman W.G. Jr.
    J. Biol. Chem. 269:24384-24390(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, COFACTOR.
    Strain: K12.
  9. "The rfaD gene codes for ADP-L-glycero-D-mannoheptose-6-epimerase. An enzyme required for lipopolysaccharide core biosynthesis."
    Coleman W.G. Jr.
    J. Biol. Chem. 258:1985-1990(1983) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
    Strain: K12.
  10. "Crystallization and preliminary X-ray diffraction studies of the lipopolysaccharide core biosynthetic enzyme ADP-L-glycero-D-mannoheptose 6-epimerase from Escherichia coli K-12."
    Ding L., Zhang Y., Deacon A.M., Ealick S.E., Ni Y.S., Sun P., Coleman W.G. Jr.
    Acta Crystallogr. D 55:685-688(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: CRYSTALLIZATION.
  11. "Evidence that NADP+ is the physiological cofactor of ADP-L-glycero-D-mannoheptose 6-epimerase."
    Ni Y.S., McPhie P., Deacon A.M., Ealick S.E., Coleman W.G. Jr.
    J. Biol. Chem. 276:27329-27334(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: COFACTOR.
  12. "Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli."
    Kneidinger B., Marolda C., Graninger M., Zamyatina A., McArthur F., Kosma P., Valvano M.A., Messner P.
    J. Bacteriol. 184:363-369(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: ADP-L-GLYCERO-BETA-D-MANNO-HEPTOSE BIOSYNTHESIS PATHWAY.
    Strain: K12 / MG1655 / ATCC 47076.
  13. "A two-base mechanism for Escherichia coli ADP-L-glycero-D-manno-heptose 6-epimerase."
    Morrison J.P., Tanner M.E.
    Biochemistry 46:3916-3924(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF TYR-140; LYS-178; LYS-208 AND ASP-210, REACTION MECHANISM, ACTIVE SITE.
  14. "Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli."
    Zhang J., Sprung R., Pei J., Tan X., Kim S., Zhu H., Liu C.F., Grishin N.V., Zhao Y.
    Mol. Cell. Proteomics 8:215-225(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-267, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: K12 / JW1106 and K12 / MG1655 / ATCC 47076.
  15. "The crystal structure of ADP-L-glycero-D-mannoheptose 6-epimerase: catalysis with a twist."
    Deacon A.M., Ni Y.S., Coleman W.G. Jr., Ealick S.E.
    Structure 8:453-462(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF COMPLEX WITH NADP AND ADP-GLUCOSE, SUBUNIT.

Entry informationi

Entry nameiHLDD_ECOLI
AccessioniPrimary (citable) accession number: P67910
Secondary accession number(s): P17963, Q2M7T3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: March 16, 2016
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

Essential for E.coli viability at elevated temperatures. Insertional inactivation of the gene by the Tn5 transposon results in E.coli being unable to form colonies at temperatures above 43 degrees Celsius.

Caution

Was originally thought to be a homohexamer.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.