DAPB_ECOLI
ID DAPB_ECOLI Reviewed; 273 AA.
AC P04036;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1986, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=4-hydroxy-tetrahydrodipicolinate reductase {ECO:0000255|HAMAP-Rule:MF_00102};
DE Short=HTPA reductase {ECO:0000255|HAMAP-Rule:MF_00102};
DE EC=1.17.1.8 {ECO:0000255|HAMAP-Rule:MF_00102};
GN Name=dapB {ECO:0000255|HAMAP-Rule:MF_00102};
GN OrderedLocusNames=b0031, JW0029;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6094578; DOI=10.1016/s0021-9258(17)42678-0;
RA Bouvier J., Richaud C., Richaud F., Patte J.-C., Stragier P.;
RT "Nucleotide sequence and expression of the Escherichia coli dapB gene.";
RL J. Biol. Chem. 259:14829-14834(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=1630901; DOI=10.1093/nar/20.13.3305;
RA Yura T., Mori H., Nagai H., Nagata T., Ishihama A., Fujita N., Isono K.,
RA Mizobuchi K., Nakata A.;
RT "Systematic sequencing of the Escherichia coli genome: analysis of the 0-
RT 2.4 min region.";
RL Nucleic Acids Res. 20:3305-3308(1992).
RN [3]
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 269-273.
RX PubMed=6377309; DOI=10.1073/pnas.81.13.4139;
RA Bouvier J., Patte J.-C., Stragier P.;
RT "Multiple regulatory signals in the control region of the Escherichia coli
RT carAB operon.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:4139-4143(1984).
RN [6]
RP PROTEIN SEQUENCE OF 1-18, FUNCTION, KINETIC PARAMETERS, SUBSTRATE
RP SPECIFICITY, SUBUNIT, AND MASS SPECTROMETRY.
RC STRAIN=K12;
RX PubMed=7893644; DOI=10.1021/bi00011a002;
RA Reddy S.G., Sacchettini J.C., Blanchard J.S.;
RT "Expression, purification, and characterization of Escherichia coli
RT dihydrodipicolinate reductase.";
RL Biochemistry 34:3492-3501(1995).
RN [7]
RP INDUCTION.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=18502871; DOI=10.1128/jb.01782-07;
RA Bouvier J., Stragier P., Morales V., Remy E., Gutierrez C.;
RT "Lysine represses transcription of the Escherichia coli dapB gene by
RT preventing its activation by the ArgP activator.";
RL J. Bacteriol. 190:5224-5229(2008).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION OF HTPA AS REACTION
RP SUBSTRTATE, AND ACTIVE SITE.
RX PubMed=20503968; DOI=10.1021/jm100349s;
RA Devenish S.R., Blunt J.W., Gerrard J.A.;
RT "NMR studies uncover alternate substrates for dihydrodipicolinate synthase
RT and suggest that dihydrodipicolinate reductase is also a dehydratase.";
RL J. Med. Chem. 53:4808-4812(2010).
RN [9] {ECO:0007744|PDB:1DIH}
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH NADPH.
RC STRAIN=K12;
RX PubMed=7893645; DOI=10.1021/bi00011a003;
RA Scapin G., Blanchard J.S., Sacchettini J.C.;
RT "Three-dimensional structure of Escherichia coli dihydrodipicolinate
RT reductase.";
RL Biochemistry 34:3502-3512(1995).
RN [10] {ECO:0007744|PDB:1DRU, ECO:0007744|PDB:1DRV, ECO:0007744|PDB:1DRW}
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH NAD OR NUCLEOTIDE
RP SUBSTRATE ANALOGS.
RC STRAIN=K12;
RX PubMed=8873595; DOI=10.1021/bi9615809;
RA Reddy S.G., Scapin G., Blanchard J.S.;
RT "Interaction of pyridine nucleotide substrates with Escherichia coli
RT dihydrodipicolinate reductase: thermodynamic and structural analysis of
RT binary complexes.";
RL Biochemistry 35:13294-13302(1996).
RN [11] {ECO:0007744|PDB:1ARZ}
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH NAD AND A SUBSTRATE
RP ANALOG INHIBITOR, ACTIVITY REGULATION, KINETIC PARAMETERS, REACTION
RP MECHANISM, ACTIVE SITE, SITE, AND MUTAGENESIS OF HIS-159 AND LYS-163.
RC STRAIN=K12;
RX PubMed=9398235; DOI=10.1021/bi9719915;
RA Scapin G., Reddy S.G., Zheng R., Blanchard J.S.;
RT "Three-dimensional structure of Escherichia coli dihydrodipicolinate
RT reductase in complex with NADH and the inhibitor 2,6-
RT pyridinedicarboxylate.";
RL Biochemistry 36:15081-15088(1997).
CC -!- FUNCTION: Catalyzes the conversion of 4-hydroxy-tetrahydrodipicolinate
CC (HTPA) to tetrahydrodipicolinate. Can use both NADH and NADPH as a
CC reductant, with NADH being twice as effective as NADPH.
CC {ECO:0000255|HAMAP-Rule:MF_00102, ECO:0000269|PubMed:20503968,
CC ECO:0000269|PubMed:7893644}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-2,3,4,5-tetrahydrodipicolinate + H2O + NAD(+) = (2S,4S)-4-
CC hydroxy-2,3,4,5-tetrahydrodipicolinate + H(+) + NADH;
CC Xref=Rhea:RHEA:35323, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16845, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:67139; EC=1.17.1.8; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_00102, ECO:0000269|PubMed:20503968};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-2,3,4,5-tetrahydrodipicolinate + H2O + NADP(+) = (2S,4S)-
CC 4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H(+) + NADPH;
CC Xref=Rhea:RHEA:35331, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16845, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:67139; EC=1.17.1.8; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_00102, ECO:0000269|PubMed:20503968};
CC -!- ACTIVITY REGULATION: Is inhibited by 2,6-pyridine dicarboxylate (2,6-
CC PDC or picolinate). {ECO:0000269|PubMed:9398235}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.6 uM for NADH {ECO:0000269|PubMed:7893644,
CC ECO:0000269|PubMed:9398235};
CC KM=8 uM for NADPH {ECO:0000269|PubMed:7893644,
CC ECO:0000269|PubMed:9398235};
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via DAP
CC pathway; (S)-tetrahydrodipicolinate from L-aspartate: step 4/4.
CC {ECO:0000255|HAMAP-Rule:MF_00102}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_00102,
CC ECO:0000269|PubMed:7893644, ECO:0000269|PubMed:7893645,
CC ECO:0000269|PubMed:8873595, ECO:0000269|PubMed:9398235}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- INDUCTION: Expression of dapB is up-regulated by ArgP and is repressed
CC by lysine that prevents the binding of the ArgP activator. Thus, ArgP
CC contributes to enhanced transcription of dapB when lysine becomes
CC limiting. {ECO:0000269|PubMed:18502871}.
CC -!- MASS SPECTROMETRY: Mass=28758; Mass_error=8; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:7893644};
CC -!- SIMILARITY: Belongs to the DapB family. {ECO:0000255|HAMAP-
CC Rule:MF_00102}.
CC -!- CAUTION: Was originally thought to be a dihydrodipicolinate reductase
CC (DHDPR), catalyzing the conversion of dihydrodipicolinate to
CC tetrahydrodipicolinate. However, it was shown that the substrate of the
CC enzymatic reaction is not dihydrodipicolinate (DHDP) but in fact
CC (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid (HTPA), the
CC product released by the DapA-catalyzed reaction (PubMed:20503968).
CC {ECO:0000305|PubMed:20503968}.
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DR EMBL; M10611; AAA23666.1; -; Genomic_DNA.
DR EMBL; U00096; AAC73142.1; -; Genomic_DNA.
DR EMBL; AP009048; BAB96600.1; -; Genomic_DNA.
DR EMBL; J01597; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A00375; RDECPD.
DR RefSeq; NP_414572.1; NC_000913.3.
DR RefSeq; WP_000543604.1; NZ_SSUR01000014.1.
DR PDB; 1ARZ; X-ray; 2.60 A; A/B/C/D=1-273.
DR PDB; 1DIH; X-ray; 2.20 A; A=1-273.
DR PDB; 1DRU; X-ray; 2.20 A; A=1-273.
DR PDB; 1DRV; X-ray; 2.20 A; A=1-273.
DR PDB; 1DRW; X-ray; 2.20 A; A=1-273.
DR PDBsum; 1ARZ; -.
DR PDBsum; 1DIH; -.
DR PDBsum; 1DRU; -.
DR PDBsum; 1DRV; -.
DR PDBsum; 1DRW; -.
DR AlphaFoldDB; P04036; -.
DR SMR; P04036; -.
DR BioGRID; 4261490; 16.
DR DIP; DIP-9399N; -.
DR IntAct; P04036; 1.
DR STRING; 511145.b0031; -.
DR BindingDB; P04036; -.
DR ChEMBL; CHEMBL3309005; -.
DR DrugBank; DB03363; 3-Acetylpyridine Adenine Dinucleotide.
DR DrugBank; DB04267; Dipicolinic acid.
DR SWISS-2DPAGE; P04036; -.
DR jPOST; P04036; -.
DR PaxDb; P04036; -.
DR PRIDE; P04036; -.
DR EnsemblBacteria; AAC73142; AAC73142; b0031.
DR EnsemblBacteria; BAB96600; BAB96600; BAB96600.
DR GeneID; 944762; -.
DR KEGG; ecj:JW0029; -.
DR KEGG; eco:b0031; -.
DR PATRIC; fig|1411691.4.peg.2254; -.
DR EchoBASE; EB0202; -.
DR eggNOG; COG0289; Bacteria.
DR HOGENOM; CLU_047479_2_1_6; -.
DR InParanoid; P04036; -.
DR OMA; HHPNKAD; -.
DR PhylomeDB; P04036; -.
DR BioCyc; EcoCyc:DIHYDROPICRED-MON; -.
DR BioCyc; MetaCyc:DIHYDROPICRED-MON; -.
DR BRENDA; 1.17.1.8; 2026.
DR SABIO-RK; P04036; -.
DR UniPathway; UPA00034; UER00018.
DR EvolutionaryTrace; P04036; -.
DR PRO; PR:P04036; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0008839; F:4-hydroxy-tetrahydrodipicolinate reductase; IDA:EcoCyc.
DR GO; GO:0042802; F:identical protein binding; IDA:EcoCyc.
DR GO; GO:0051287; F:NAD binding; IEA:UniProtKB-UniRule.
DR GO; GO:0050661; F:NADP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0016726; F:oxidoreductase activity, acting on CH or CH2 groups, NAD or NADP as acceptor; IEA:UniProtKB-UniRule.
DR GO; GO:0008652; P:cellular amino acid biosynthetic process; IDA:EcoliWiki.
DR GO; GO:0019877; P:diaminopimelate biosynthetic process; IDA:EcoliWiki.
DR GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IEA:UniProtKB-UniRule.
DR HAMAP; MF_00102; DapB; 1.
DR InterPro; IPR022663; DapB_C.
DR InterPro; IPR000846; DapB_N.
DR InterPro; IPR022664; DapB_N_CS.
DR InterPro; IPR023940; DHDPR_bac.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR PANTHER; PTHR20836; PTHR20836; 1.
DR Pfam; PF05173; DapB_C; 1.
DR Pfam; PF01113; DapB_N; 1.
DR PIRSF; PIRSF000161; DHPR; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR00036; dapB; 1.
DR PROSITE; PS01298; DAPB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Cytoplasm;
KW Diaminopimelate biosynthesis; Direct protein sequencing;
KW Lysine biosynthesis; NAD; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..273
FT /note="4-hydroxy-tetrahydrodipicolinate reductase"
FT /id="PRO_0000141437"
FT ACT_SITE 159
FT /note="Proton donor/acceptor"
FT ACT_SITE 163
FT /note="Proton donor"
FT BINDING 12
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:7893645,
FT ECO:0007744|PDB:1DIH"
FT BINDING 15..17
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:8873595,
FT ECO:0000269|PubMed:9398235, ECO:0007744|PDB:1ARZ,
FT ECO:0007744|PDB:1DRU"
FT BINDING 16..17
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:7893645,
FT ECO:0007744|PDB:1DIH"
FT BINDING 38
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:8873595,
FT ECO:0000269|PubMed:9398235, ECO:0007744|PDB:1ARZ,
FT ECO:0007744|PDB:1DRU"
FT BINDING 39
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:7893645,
FT ECO:0007744|PDB:1DIH"
FT BINDING 80..81
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:8873595,
FT ECO:0000269|PubMed:9398235, ECO:0007744|PDB:1ARZ,
FT ECO:0007744|PDB:1DRU"
FT BINDING 102..104
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:8873595,
FT ECO:0000269|PubMed:9398235, ECO:0007744|PDB:1ARZ,
FT ECO:0007744|PDB:1DRU"
FT BINDING 102..104
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:7893645,
FT ECO:0007744|PDB:1DIH"
FT BINDING 126..129
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:8873595,
FT ECO:0000269|PubMed:9398235, ECO:0007744|PDB:1ARZ,
FT ECO:0007744|PDB:1DRU"
FT BINDING 129
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:7893645,
FT ECO:0007744|PDB:1DIH"
FT BINDING 160
FT /ligand="(S)-2,3,4,5-tetrahydrodipicolinate"
FT /ligand_id="ChEBI:CHEBI:16845"
FT BINDING 163
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:9398235,
FT ECO:0007744|PDB:1ARZ"
FT BINDING 169..170
FT /ligand="(S)-2,3,4,5-tetrahydrodipicolinate"
FT /ligand_id="ChEBI:CHEBI:16845"
FT BINDING 240
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:7893645,
FT ECO:0007744|PDB:1DIH"
FT BINDING 243
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:9398235,
FT ECO:0007744|PDB:1ARZ"
FT MUTAGEN 159
FT /note="H->A,Q: 135 to 200-fold reduction in catalytic
FT activity."
FT /evidence="ECO:0000269|PubMed:9398235"
FT MUTAGEN 163
FT /note="K->A,C,Q: 625 to 830-fold reduction in catalytic
FT activity."
FT /evidence="ECO:0000269|PubMed:9398235"
FT STRAND 5..10
FT /evidence="ECO:0007829|PDB:1DIH"
FT TURN 11..14
FT /evidence="ECO:0007829|PDB:1DIH"
FT HELIX 16..27
FT /evidence="ECO:0007829|PDB:1DIH"
FT STRAND 32..37
FT /evidence="ECO:0007829|PDB:1DRU"
FT TURN 44..47
FT /evidence="ECO:0007829|PDB:1DRU"
FT STRAND 52..56
FT /evidence="ECO:0007829|PDB:1DIH"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:1DIH"
FT TURN 67..71
FT /evidence="ECO:0007829|PDB:1DIH"
FT STRAND 74..78
FT /evidence="ECO:0007829|PDB:1DIH"
FT HELIX 82..94
FT /evidence="ECO:0007829|PDB:1DIH"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:1DIH"
FT HELIX 108..117
FT /evidence="ECO:0007829|PDB:1DIH"
FT TURN 118..120
FT /evidence="ECO:0007829|PDB:1DIH"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:1DIH"
FT HELIX 131..147
FT /evidence="ECO:0007829|PDB:1DIH"
FT TURN 148..150
FT /evidence="ECO:0007829|PDB:1DIH"
FT STRAND 151..159
FT /evidence="ECO:0007829|PDB:1DIH"
FT STRAND 165..167
FT /evidence="ECO:0007829|PDB:1DIH"
FT HELIX 169..181
FT /evidence="ECO:0007829|PDB:1DIH"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:1DIH"
FT STRAND 206..212
FT /evidence="ECO:0007829|PDB:1DIH"
FT STRAND 218..226
FT /evidence="ECO:0007829|PDB:1DIH"
FT STRAND 229..237
FT /evidence="ECO:0007829|PDB:1DIH"
FT HELIX 241..254
FT /evidence="ECO:0007829|PDB:1DIH"
FT STRAND 259..262
FT /evidence="ECO:0007829|PDB:1DIH"
FT HELIX 264..267
FT /evidence="ECO:0007829|PDB:1DIH"
FT HELIX 270..272
FT /evidence="ECO:0007829|PDB:1DIH"
SQ SEQUENCE 273 AA; 28757 MW; 0ADE6837A6CF932C CRC64;
MHDANIRVAI AGAGGRMGRQ LIQAALALEG VQLGAALERE GSSLLGSDAG ELAGAGKTGV
TVQSSLDAVK DDFDVFIDFT RPEGTLNHLA FCRQHGKGMV IGTTGFDEAG KQAIRDAAAD
IAIVFAANFS VGVNVMLKLL EKAAKVMGDY TDIEIIEAHH RHKVDAPSGT ALAMGEAIAH
ALDKDLKDCA VYSREGHTGE RVPGTIGFAT VRAGDIVGEH TAMFADIGER LEITHKASSR
MTFANGAVRS ALWLSGKESG LFDMRDVLDL NNL
