HLDD_ECOLI
ID HLDD_ECOLI Reviewed; 310 AA.
AC P67910; P17963; Q2M7T3;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=ADP-L-glycero-D-manno-heptose-6-epimerase;
DE EC=5.1.3.20 {ECO:0000269|PubMed:7929099};
DE AltName: Full=ADP-L-glycero-beta-D-manno-heptose-6-epimerase;
DE Short=ADP-glyceromanno-heptose 6-epimerase;
DE Short=ADP-hep 6-epimerase;
DE Short=AGME;
GN Name=hldD; Synonyms=htrM, rfaD, waaD; OrderedLocusNames=b3619, JW3594;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 1-34.
RC STRAIN=K12;
RX PubMed=2198271; DOI=10.1128/jb.172.8.4652-4660.1990;
RA Pegues J.C., Chen L., Gordon A.W., Ding L., Coleman W.G. Jr.;
RT "Cloning, expression, and characterization of the Escherichia coli K-12
RT rfaD gene.";
RL J. Bacteriol. 172:4652-4660(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=1861974; DOI=10.1093/nar/19.14.3811;
RA Raina S., Georgopoulos C.;
RT "The htrM gene, whose product is essential for Escherichia coli viability
RT only at elevated temperatures, is identical to the rfaD gene.";
RL Nucleic Acids Res. 19:3811-3819(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=8041620; DOI=10.1093/nar/22.13.2576;
RA Sofia H.J., Burland V., Daniels D.L., Plunkett G. III, Blattner F.R.;
RT "Analysis of the Escherichia coli genome. V. DNA sequence of the region
RT from 76.0 to 81.5 minutes.";
RL Nucleic Acids Res. 22:2576-2586(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [6]
RP PROTEIN SEQUENCE OF 1-12.
RC STRAIN=K12 / EMG2;
RX PubMed=9298646; DOI=10.1002/elps.1150180807;
RA Link A.J., Robison K., Church G.M.;
RT "Comparing the predicted and observed properties of proteins encoded in the
RT genome of Escherichia coli K-12.";
RL Electrophoresis 18:1259-1313(1997).
RN [7]
RP PROTEIN SEQUENCE OF 1-11.
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RA Frutiger S., Hughes G.J., Pasquali C., Hochstrasser D.F.;
RL Submitted (FEB-1996) to UniProtKB.
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND
RP COFACTOR.
RC STRAIN=K12;
RX PubMed=7929099; DOI=10.1016/s0021-9258(19)51095-x;
RA Ding L., Seto B.L., Ahmed S.A., Coleman W.G. Jr.;
RT "Purification and properties of the Escherichia coli K-12 NAD-dependent
RT nucleotide diphosphosugar epimerase, ADP-L-glycero-D-mannoheptose 6-
RT epimerase.";
RL J. Biol. Chem. 269:24384-24390(1994).
RN [9]
RP FUNCTION.
RC STRAIN=K12;
RX PubMed=6337148; DOI=10.1016/s0021-9258(18)33085-0;
RA Coleman W.G. Jr.;
RT "The rfaD gene codes for ADP-L-glycero-D-mannoheptose-6-epimerase. An
RT enzyme required for lipopolysaccharide core biosynthesis.";
RL J. Biol. Chem. 258:1985-1990(1983).
RN [10]
RP CRYSTALLIZATION.
RX PubMed=10089470; DOI=10.1107/s0907444998014723;
RA Ding L., Zhang Y., Deacon A.M., Ealick S.E., Ni Y.S., Sun P.,
RA Coleman W.G. Jr.;
RT "Crystallization and preliminary X-ray diffraction studies of the
RT lipopolysaccharide core biosynthetic enzyme ADP-L-glycero-D-mannoheptose 6-
RT epimerase from Escherichia coli K-12.";
RL Acta Crystallogr. D 55:685-688(1999).
RN [11]
RP COFACTOR.
RX PubMed=11313358; DOI=10.1074/jbc.m102258200;
RA Ni Y.S., McPhie P., Deacon A.M., Ealick S.E., Coleman W.G. Jr.;
RT "Evidence that NADP+ is the physiological cofactor of ADP-L-glycero-D-
RT mannoheptose 6-epimerase.";
RL J. Biol. Chem. 276:27329-27334(2001).
RN [12]
RP ADP-L-GLYCERO-BETA-D-MANNO-HEPTOSE BIOSYNTHESIS PATHWAY.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=11751812; DOI=10.1128/jb.184.2.363-369.2002;
RA Kneidinger B., Marolda C., Graninger M., Zamyatina A., McArthur F.,
RA Kosma P., Valvano M.A., Messner P.;
RT "Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia
RT coli.";
RL J. Bacteriol. 184:363-369(2002).
RN [13]
RP MUTAGENESIS OF TYR-140; LYS-178; LYS-208 AND ASP-210, REACTION MECHANISM,
RP AND ACTIVE SITE.
RX PubMed=17316025; DOI=10.1021/bi602641m;
RA Morrison J.P., Tanner M.E.;
RT "A two-base mechanism for Escherichia coli ADP-L-glycero-D-manno-heptose 6-
RT epimerase.";
RL Biochemistry 46:3916-3924(2007).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-267, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=K12 / JW1106, and K12 / MG1655 / ATCC 47076;
RX PubMed=18723842; DOI=10.1074/mcp.m800187-mcp200;
RA Zhang J., Sprung R., Pei J., Tan X., Kim S., Zhu H., Liu C.F.,
RA Grishin N.V., Zhao Y.;
RT "Lysine acetylation is a highly abundant and evolutionarily conserved
RT modification in Escherichia coli.";
RL Mol. Cell. Proteomics 8:215-225(2009).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF COMPLEX WITH NADP AND ADP-GLUCOSE,
RP AND SUBUNIT.
RX PubMed=10896473; DOI=10.1016/s0969-2126(00)00128-3;
RA Deacon A.M., Ni Y.S., Coleman W.G. Jr., Ealick S.E.;
RT "The crystal structure of ADP-L-glycero-D-mannoheptose 6-epimerase:
RT catalysis with a twist.";
RL Structure 8:453-462(2000).
CC -!- FUNCTION: Catalyzes the interconversion between ADP-D-glycero-beta-D-
CC manno-heptose and ADP-L-glycero-beta-D-manno-heptose via an
CC epimerization at carbon 6 of the heptose. {ECO:0000269|PubMed:6337148,
CC ECO:0000269|PubMed:7929099}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ADP-D-glycero-beta-D-manno-heptose = ADP-L-glycero-beta-D-
CC manno-heptose; Xref=Rhea:RHEA:17577, ChEBI:CHEBI:59967,
CC ChEBI:CHEBI:61506; EC=5.1.3.20;
CC Evidence={ECO:0000269|PubMed:7929099};
CC -!- COFACTOR:
CC Name=NADP(+); Xref=ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:11313358, ECO:0000269|PubMed:7929099};
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000269|PubMed:11313358, ECO:0000269|PubMed:7929099};
CC Note=Binds 1 NADP(+) per subunit. NAD(+) can substitute for NADP(+),
CC but enzymatic activity is reduced. {ECO:0000269|PubMed:11313358,
CC ECO:0000269|PubMed:7929099};
CC -!- ACTIVITY REGULATION: Completely inhibited by ADP and ADP-glucose, and
CC partially inhibited by ATP and NADH.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.1 mM for ADP-heptose {ECO:0000269|PubMed:7929099};
CC Vmax=1.53 umol/min/mg enzyme {ECO:0000269|PubMed:7929099};
CC pH dependence:
CC Optimum pH is 5.5-9.5. {ECO:0000269|PubMed:7929099};
CC Temperature dependence:
CC Optimum temperature is 42 degrees Celsius.
CC {ECO:0000269|PubMed:7929099};
CC -!- PATHWAY: Nucleotide-sugar biosynthesis; ADP-L-glycero-beta-D-manno-
CC heptose biosynthesis; ADP-L-glycero-beta-D-manno-heptose from D-
CC glycero-beta-D-manno-heptose 7-phosphate: step 4/4.
CC -!- PATHWAY: Bacterial outer membrane biogenesis; LPS core biosynthesis.
CC -!- SUBUNIT: Homopentamer. {ECO:0000269|PubMed:10896473,
CC ECO:0000269|PubMed:7929099}.
CC -!- INTERACTION:
CC P67910; P16528: iclR; NbExp=2; IntAct=EBI-543760, EBI-552904;
CC P67910; P62617: ispF; NbExp=2; IntAct=EBI-543760, EBI-562321;
CC P67910; P0ABU0: menB; NbExp=3; IntAct=EBI-543760, EBI-554195;
CC P67910; P25534: ubiH; NbExp=2; IntAct=EBI-543760, EBI-559377;
CC P67910; P0A8C1: ybjQ; NbExp=2; IntAct=EBI-543760, EBI-544395;
CC -!- INDUCTION: By heat shock.
CC -!- DOMAIN: Contains a large N-terminal NADP-binding domain associated with
CC a modified Rossman fold, and a smaller C-terminal substrate-binding
CC domain.
CC -!- MISCELLANEOUS: Essential for E.coli viability at elevated temperatures.
CC Insertional inactivation of the gene by the Tn5 transposon results in
CC E.coli being unable to form colonies at temperatures above 43 degrees
CC Celsius.
CC -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase
CC family. HldD subfamily. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be a homohexamer.
CC {ECO:0000305|PubMed:7929099}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M33577; AAA24525.1; -; Genomic_DNA.
DR EMBL; X54492; CAA38364.1; -; Genomic_DNA.
DR EMBL; U00039; AAB18596.1; -; Genomic_DNA.
DR EMBL; U00096; AAC76643.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE77673.1; -; Genomic_DNA.
DR PIR; JU0299; JU0299.
DR RefSeq; NP_418076.1; NC_000913.3.
DR RefSeq; WP_000587764.1; NZ_LN832404.1.
DR PDB; 1EQ2; X-ray; 2.00 A; A/B/C/D/E/F/G/H/I/J=1-310.
DR PDB; 2X6T; X-ray; 2.36 A; A/B/C/D/E/F/G/H/I/J=1-310.
DR PDBsum; 1EQ2; -.
DR PDBsum; 2X6T; -.
DR AlphaFoldDB; P67910; -.
DR SMR; P67910; -.
DR BioGRID; 4263293; 559.
DR DIP; DIP-35958N; -.
DR IntAct; P67910; 40.
DR STRING; 511145.b3619; -.
DR DrugBank; DB01774; Adenosine-5'-Monophosphate Glucopyranosyl-Monophosphate Ester.
DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate.
DR iPTMnet; P67910; -.
DR SWISS-2DPAGE; P67910; -.
DR jPOST; P67910; -.
DR PaxDb; P67910; -.
DR PRIDE; P67910; -.
DR EnsemblBacteria; AAC76643; AAC76643; b3619.
DR EnsemblBacteria; BAE77673; BAE77673; BAE77673.
DR GeneID; 67417621; -.
DR GeneID; 948134; -.
DR KEGG; ecj:JW3594; -.
DR KEGG; eco:b3619; -.
DR PATRIC; fig|1411691.4.peg.3087; -.
DR EchoBASE; EB0831; -.
DR eggNOG; COG0451; Bacteria.
DR HOGENOM; CLU_007383_1_3_6; -.
DR InParanoid; P67910; -.
DR OMA; LRDFVYI; -.
DR PhylomeDB; P67910; -.
DR BioCyc; EcoCyc:EG10838-MON; -.
DR BioCyc; MetaCyc:EG10838-MON; -.
DR BRENDA; 5.1.3.20; 2026.
DR SABIO-RK; P67910; -.
DR UniPathway; UPA00356; UER00440.
DR UniPathway; UPA00958; -.
DR EvolutionaryTrace; P67910; -.
DR PRO; PR:P67910; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0008712; F:ADP-glyceromanno-heptose 6-epimerase activity; IDA:EcoCyc.
DR GO; GO:0070401; F:NADP+ binding; IDA:EcoCyc.
DR GO; GO:0097171; P:ADP-L-glycero-beta-D-manno-heptose biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009244; P:lipopolysaccharide core region biosynthetic process; IMP:EcoCyc.
DR CDD; cd05248; ADP_GME_SDR_e; 1.
DR HAMAP; MF_01601; Heptose_epimerase; 1.
DR InterPro; IPR001509; Epimerase_deHydtase.
DR InterPro; IPR011912; Heptose_epim.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01370; Epimerase; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR02197; heptose_epim; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Carbohydrate metabolism;
KW Direct protein sequencing; Isomerase; Lipopolysaccharide biosynthesis; NAD;
KW NADP; Reference proteome; Stress response.
FT CHAIN 1..310
FT /note="ADP-L-glycero-D-manno-heptose-6-epimerase"
FT /id="PRO_0000205793"
FT ACT_SITE 140
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:17316025"
FT ACT_SITE 178
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:17316025"
FT BINDING 10..11
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10896473"
FT BINDING 31..32
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10896473"
FT BINDING 38
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10896473"
FT BINDING 53
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10896473"
FT BINDING 75..79
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10896473"
FT BINDING 92
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10896473"
FT BINDING 144
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10896473"
FT BINDING 169
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10896473"
FT BINDING 170
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10896473"
FT BINDING 178
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10896473"
FT BINDING 180
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10896473"
FT BINDING 187
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10896473"
FT BINDING 201..204
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10896473"
FT BINDING 209
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10896473"
FT BINDING 272
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10896473"
FT MOD_RES 267
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:18723842"
FT MUTAGEN 140
FT /note="Y->F: Severely compromises epimerase activity."
FT /evidence="ECO:0000269|PubMed:17316025"
FT MUTAGEN 178
FT /note="K->M: Severely compromises epimerase activity."
FT /evidence="ECO:0000269|PubMed:17316025"
FT MUTAGEN 208
FT /note="K->M: Activity similar to that of the wild-type."
FT /evidence="ECO:0000269|PubMed:17316025"
FT MUTAGEN 210
FT /note="D->N: Activity similar to that of the wild-type."
FT /evidence="ECO:0000269|PubMed:17316025"
FT STRAND 2..5
FT /evidence="ECO:0007829|PDB:1EQ2"
FT TURN 6..8
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 10..20
FT /evidence="ECO:0007829|PDB:1EQ2"
FT TURN 21..23
FT /evidence="ECO:0007829|PDB:1EQ2"
FT STRAND 27..31
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 36..39
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 40..43
FT /evidence="ECO:0007829|PDB:1EQ2"
FT STRAND 48..52
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 53..61
FT /evidence="ECO:0007829|PDB:1EQ2"
FT STRAND 71..74
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 86..92
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 94..107
FT /evidence="ECO:0007829|PDB:1EQ2"
FT STRAND 111..116
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 117..120
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 131..133
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 139..154
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:1EQ2"
FT STRAND 162..167
FT /evidence="ECO:0007829|PDB:1EQ2"
FT STRAND 169..174
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 176..181
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 184..193
FT /evidence="ECO:0007829|PDB:1EQ2"
FT STRAND 199..203
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:2X6T"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 214..227
FT /evidence="ECO:0007829|PDB:1EQ2"
FT STRAND 231..236
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 243..249
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 251..254
FT /evidence="ECO:0007829|PDB:1EQ2"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 266..268
FT /evidence="ECO:0007829|PDB:1EQ2"
FT TURN 269..271
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 281..285
FT /evidence="ECO:0007829|PDB:1EQ2"
FT HELIX 295..305
FT /evidence="ECO:0007829|PDB:1EQ2"
SQ SEQUENCE 310 AA; 34893 MW; 4B9388A879CB7522 CRC64;
MIIVTGGAGF IGSNIVKALN DKGITDILVV DNLKDGTKFV NLVDLNIADY MDKEDFLIQI
MAGEEFGDVE AIFHEGACSS TTEWDGKYMM DNNYQYSKEL LHYCLEREIP FLYASSAATY
GGRTSDFIES REYEKPLNVY GYSKFLFDEY VRQILPEANS QIVGFRYFNV YGPREGHKGS
MASVAFHLNT QLNNGESPKL FEGSENFKRD FVYVGDVADV NLWFLENGVS GIFNLGTGRA
ESFQAVADAT LAYHKKGQIE YIPFPDKLKG RYQAFTQADL TNLRAAGYDK PFKTVAEGVT
EYMAWLNRDA
