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Protein

4-hydroxy-tetrahydrodipicolinate synthase

Gene

dapA

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

Functioni

Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).UniRule annotation2 Publications

Catalytic activityi

Pyruvate + L-aspartate-4-semialdehyde = (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinate + H2O.UniRule annotation2 Publications

Enzyme regulationi

Is allosterically regulated by the feedback inhibitor (S)-lysine. Is inhibited by pyruvate analogs such as 3-fluoropyruvate, 2-ketobutyrate, glyoxylate, and beta-hydroxypyruvate. Is not inhibited by its substrate, (S)-ASA.3 Publications

Kineticsi

kcat is 124 sec(-1).

  1. KM=0.26 mM for pyruvate2 Publications
  2. KM=0.11 mM for L-aspartate-4-semialdehyde2 Publications
  1. Vmax=0.58 µmol/sec/mg enzyme2 Publications

Pathwayi: L-lysine biosynthesis via DAP pathway

This protein is involved in step 3 of the subpathway that synthesizes (S)-tetrahydrodipicolinate from L-aspartate.UniRule annotation
Proteins known to be involved in the 4 steps of the subpathway in this organism are:
  1. Lysine-sensitive aspartokinase 3 (lysC), Bifunctional aspartokinase/homoserine dehydrogenase 1 (thrA), Bifunctional aspartokinase/homoserine dehydrogenase 2 (metL)
  2. Aspartate-semialdehyde dehydrogenase (asd)
  3. 4-hydroxy-tetrahydrodipicolinate synthase (dapA)
  4. 4-hydroxy-tetrahydrodipicolinate reductase (dapB)
This subpathway is part of the pathway L-lysine biosynthesis via DAP pathway, which is itself part of Amino-acid biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes (S)-tetrahydrodipicolinate from L-aspartate, the pathway L-lysine biosynthesis via DAP pathway and in Amino-acid biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei44Part of a proton relay during catalysis1
Binding sitei45PyruvateUniRule annotation2 Publications1
Sitei49L-lysine inhibitor binding; via carbonyl oxygen1
Sitei80L-lysine inhibitor binding1
Sitei84L-lysine inhibitor binding1
Sitei106L-lysine inhibitor binding1
Sitei107Part of a proton relay during catalysis1
Active sitei133Proton donor/acceptor1
Active sitei161Schiff-base intermediate with substrate1
Binding sitei203Pyruvate; via carbonyl oxygenUniRule annotation2 Publications1

GO - Molecular functioni

  • 4-hydroxy-tetrahydrodipicolinate synthase Source: EcoCyc
  • identical protein binding Source: EcoCyc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

Amino-acid biosynthesis, Diaminopimelate biosynthesis, Lysine biosynthesis

Keywords - Ligandi

Schiff base

Enzyme and pathway databases

BioCyciEcoCyc:DIHYDRODIPICSYN-MONOMER.
ECOL316407:JW2463-MONOMER.
MetaCyc:DIHYDRODIPICSYN-MONOMER.
BRENDAi4.3.3.7. 2026.
UniPathwayiUPA00034; UER00017.

Names & Taxonomyi

Protein namesi
Recommended name:
4-hydroxy-tetrahydrodipicolinate synthaseUniRule annotation (EC:4.3.3.7UniRule annotation)
Short name:
HTPA synthaseUniRule annotation
Gene namesi
Name:dapAUniRule annotation
Ordered Locus Names:b2478, JW2463
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG10205. dapA.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi44T → S: 8% of wild-type activity. 4-fold decrease in affinity for pyruvate, but nearly no change in that for (S)-ASA. 2 Publications1
Mutagenesisi44T → V: Reduced kcat by 99.9%. 2 Publications1
Mutagenesisi107Y → F: Reduced kcat by 90%. 2 Publications1
Mutagenesisi107Y → W: Reduced activity by 95%. Reduced affinity for both substrates. Exists as a mixture of monomer, dimer and tetramer in solution. Has significantly lower thermal stability than the wild-type enzyme. 2 Publications1
Mutagenesisi133Y → F: Reduced kcat by 99.7%. Reduced affinity for both substrates. 1 Publication1
Mutagenesisi138R → A or H: Strongly increased KM for L-aspartate 4-semialdehyde. No effect on KM for pyruvate. Reduced activity by 99.7%. 1 Publication1
Mutagenesisi161K → A: 0.1% of wild-type activity. 3-fold decrease in affinity for pyruvate, and 2-fold decrease in that for (S)-ASA. 1 Publication1
Mutagenesisi161K → R: 0.35% of wild-type activity. 3-fold decrease in affinity for pyruvate, but nearly no change in that for (S)-ASA. 1 Publication1
Mutagenesisi197L → Y or D: 1.4 to 2.5% of wild-type activity. Decrease in affinity for pyruvate, but nearly no change in that for (S)-ASA. Exists as a dimer in solution. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL4083.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001031101 – 2924-hydroxy-tetrahydrodipicolinate synthaseAdd BLAST292

Proteomic databases

EPDiP0A6L2.
PaxDbiP0A6L2.
PRIDEiP0A6L2.

2D gel databases

SWISS-2DPAGEP0A6L2.

Interactioni

Subunit structurei

Homotetramer; dimer of dimers.UniRule annotation6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-907527,EBI-907527

GO - Molecular functioni

  • identical protein binding Source: EcoCyc

Protein-protein interaction databases

IntActiP0A6L2. 3 interactors.
STRINGi511145.b2478.

Chemistry databases

BindingDBiP0A6L2.

Structurei

Secondary structure

1292
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi4 – 8Combined sources5
Beta strandi17 – 19Combined sources3
Helixi21 – 34Combined sources14
Beta strandi38 – 43Combined sources6
Turni44 – 47Combined sources4
Helixi48 – 50Combined sources3
Helixi53 – 67Combined sources15
Beta strandi73 – 76Combined sources4
Helixi82 – 91Combined sources10
Turni92 – 94Combined sources3
Beta strandi98 – 103Combined sources6
Helixi112 – 123Combined sources12
Beta strandi130 – 133Combined sources4
Helixi136 – 139Combined sources4
Helixi145 – 152Combined sources8
Beta strandi157 – 160Combined sources4
Helixi169 – 174Combined sources6
Beta strandi181 – 186Combined sources6
Helixi188 – 190Combined sources3
Helixi191 – 196Combined sources6
Beta strandi201 – 205Combined sources5
Helixi206 – 208Combined sources3
Helixi211 – 222Combined sources12
Helixi226 – 242Combined sources17
Beta strandi245 – 247Combined sources3
Helixi250 – 258Combined sources9
Beta strandi261 – 263Combined sources3
Helixi276 – 288Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DHPX-ray2.30A/B1-292[»]
1S5TX-ray2.30A/B1-292[»]
1S5VX-ray2.35A/B1-292[»]
1S5WX-ray2.32A/B1-292[»]
1YXCX-ray1.90A/B1-292[»]
1YXDX-ray2.00A/B1-292[»]
2A6LX-ray2.05A/B1-292[»]
2A6NX-ray1.94A/B1-292[»]
2ATSX-ray1.90A/B1-292[»]
2OJPX-ray1.70A/B1-292[»]
2PURX-ray1.70A/B1-292[»]
3C0JX-ray2.40A/B1-292[»]
3DENX-ray2.20A/B1-292[»]
3DU0X-ray2.00A/B1-292[»]
3I7QX-ray2.00A/B1-292[»]
3I7RX-ray2.10A/B1-292[»]
3I7SX-ray2.30A/B1-292[»]
4EOUX-ray2.30A/B1-292[»]
5T26X-ray2.10A/B1-292[»]
ProteinModelPortaliP0A6L2.
SMRiP0A6L2.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP0A6L2.

Family & Domainsi

Sequence similaritiesi

Belongs to the DapA family.UniRule annotation

Phylogenomic databases

eggNOGiENOG4105CDP. Bacteria.
COG0329. LUCA.
HOGENOMiHOG000173604.
InParanoidiP0A6L2.
KOiK01714.
OMAiGMDACVP.
PhylomeDBiP0A6L2.

Family and domain databases

CDDicd00950. DHDPS. 1 hit.
Gene3Di3.20.20.70. 1 hit.
HAMAPiMF_00418. DapA. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR005263. DapA.
IPR002220. DapA-like.
IPR020625. Schiff_base-form_aldolases_AS.
IPR020624. Schiff_base-form_aldolases_CS.
[Graphical view]
PANTHERiPTHR12128. PTHR12128. 1 hit.
PfamiPF00701. DHDPS. 1 hit.
[Graphical view]
PIRSFiPIRSF001365. DHDPS. 1 hit.
PRINTSiPR00146. DHPICSNTHASE.
SMARTiSM01130. DHDPS. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00674. dapA. 1 hit.
PROSITEiPS00665. DHDPS_1. 1 hit.
PS00666. DHDPS_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P0A6L2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFTGSIVAIV TPMDEKGNVC RASLKKLIDY HVASGTSAIV SVGTTGESAT
60 70 80 90 100
LNHDEHADVV MMTLDLADGR IPVIAGTGAN ATAEAISLTQ RFNDSGIVGC
110 120 130 140 150
LTVTPYYNRP SQEGLYQHFK AIAEHTDLPQ ILYNVPSRTG CDLLPETVGR
160 170 180 190 200
LAKVKNIIGI KEATGNLTRV NQIKELVSDD FVLLSGDDAS ALDFMQLGGH
210 220 230 240 250
GVISVTANVA ARDMAQMCKL AAEGHFAEAR VINQRLMPLH NKLFVEPNPI
260 270 280 290
PVKWACKELG LVATDTLRLP MTPITDSGRE TVRAALKHAG LL
Length:292
Mass (Da):31,270
Last modified:May 10, 2005 - v1
Checksum:i3970543296A77C08
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti207A → T in AAA23665 (PubMed:3514578).Curated1
Sequence conflicti224G → E in AAA23665 (PubMed:3514578).Curated1

Mass spectrometryi

Molecular mass is 31272±1 Da from positions 1 - 292. Determined by ESI. 1 Publication
Molecular mass is 31270 Da from positions 1 - 292. Determined by ESI. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12844 Genomic DNA. Translation: AAA23665.1.
U00096 Genomic DNA. Translation: AAC75531.1.
AP009048 Genomic DNA. Translation: BAA16355.1.
M33928 Genomic DNA. No translation available.
X57402 Genomic DNA. Translation: CAA40660.1.
PIRiE65023. SYECDP.
RefSeqiNP_416973.1. NC_000913.3.
WP_001311023.1. NZ_LN832404.1.

Genome annotation databases

EnsemblBacteriaiAAC75531; AAC75531; b2478.
BAA16355; BAA16355; BAA16355.
GeneIDi946952.
KEGGiecj:JW2463.
eco:b2478.
PATRICi32120343. VBIEscCol129921_2574.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12844 Genomic DNA. Translation: AAA23665.1.
U00096 Genomic DNA. Translation: AAC75531.1.
AP009048 Genomic DNA. Translation: BAA16355.1.
M33928 Genomic DNA. No translation available.
X57402 Genomic DNA. Translation: CAA40660.1.
PIRiE65023. SYECDP.
RefSeqiNP_416973.1. NC_000913.3.
WP_001311023.1. NZ_LN832404.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DHPX-ray2.30A/B1-292[»]
1S5TX-ray2.30A/B1-292[»]
1S5VX-ray2.35A/B1-292[»]
1S5WX-ray2.32A/B1-292[»]
1YXCX-ray1.90A/B1-292[»]
1YXDX-ray2.00A/B1-292[»]
2A6LX-ray2.05A/B1-292[»]
2A6NX-ray1.94A/B1-292[»]
2ATSX-ray1.90A/B1-292[»]
2OJPX-ray1.70A/B1-292[»]
2PURX-ray1.70A/B1-292[»]
3C0JX-ray2.40A/B1-292[»]
3DENX-ray2.20A/B1-292[»]
3DU0X-ray2.00A/B1-292[»]
3I7QX-ray2.00A/B1-292[»]
3I7RX-ray2.10A/B1-292[»]
3I7SX-ray2.30A/B1-292[»]
4EOUX-ray2.30A/B1-292[»]
5T26X-ray2.10A/B1-292[»]
ProteinModelPortaliP0A6L2.
SMRiP0A6L2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP0A6L2. 3 interactors.
STRINGi511145.b2478.

Chemistry databases

BindingDBiP0A6L2.
ChEMBLiCHEMBL4083.

2D gel databases

SWISS-2DPAGEP0A6L2.

Proteomic databases

EPDiP0A6L2.
PaxDbiP0A6L2.
PRIDEiP0A6L2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC75531; AAC75531; b2478.
BAA16355; BAA16355; BAA16355.
GeneIDi946952.
KEGGiecj:JW2463.
eco:b2478.
PATRICi32120343. VBIEscCol129921_2574.

Organism-specific databases

EchoBASEiEB0201.
EcoGeneiEG10205. dapA.

Phylogenomic databases

eggNOGiENOG4105CDP. Bacteria.
COG0329. LUCA.
HOGENOMiHOG000173604.
InParanoidiP0A6L2.
KOiK01714.
OMAiGMDACVP.
PhylomeDBiP0A6L2.

Enzyme and pathway databases

UniPathwayiUPA00034; UER00017.
BioCyciEcoCyc:DIHYDRODIPICSYN-MONOMER.
ECOL316407:JW2463-MONOMER.
MetaCyc:DIHYDRODIPICSYN-MONOMER.
BRENDAi4.3.3.7. 2026.

Miscellaneous databases

EvolutionaryTraceiP0A6L2.
PROiP0A6L2.

Family and domain databases

CDDicd00950. DHDPS. 1 hit.
Gene3Di3.20.20.70. 1 hit.
HAMAPiMF_00418. DapA. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR005263. DapA.
IPR002220. DapA-like.
IPR020625. Schiff_base-form_aldolases_AS.
IPR020624. Schiff_base-form_aldolases_CS.
[Graphical view]
PANTHERiPTHR12128. PTHR12128. 1 hit.
PfamiPF00701. DHDPS. 1 hit.
[Graphical view]
PIRSFiPIRSF001365. DHDPS. 1 hit.
PRINTSiPR00146. DHPICSNTHASE.
SMARTiSM01130. DHDPS. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00674. dapA. 1 hit.
PROSITEiPS00665. DHDPS_1. 1 hit.
PS00666. DHDPS_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDAPA_ECOLI
AccessioniPrimary (citable) accession number: P0A6L2
Secondary accession number(s): P05640, P78223
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: May 10, 2005
Last modified: November 30, 2016
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Caution

Was originally thought to be a dihydrodipicolinate synthase (DHDPS), catalyzing the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to dihydrodipicolinate (DHDP). However, it was shown that the product of the enzymatic reaction is not dihydrodipicolinate but in fact (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid (HTPA), and that the consecutive dehydration reaction leading to DHDP is not spontaneous but catalyzed by DapB (PubMed:8993314, PubMed:20503968).2 Publications

Keywords - Technical termi

3D-structure, Allosteric enzyme, 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.