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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)LengthDescriptionGraphical viewFeature identifierActions
Sitei44 – 441Part of a proton relay during catalysis
Binding sitei45 – 451PyruvateUniRule annotation2 Publications
Sitei49 – 491L-lysine inhibitor binding; via carbonyl oxygen
Sitei80 – 801L-lysine inhibitor binding
Sitei84 – 841L-lysine inhibitor binding
Sitei106 – 1061L-lysine inhibitor binding
Sitei107 – 1071Part of a proton relay during catalysis
Active sitei133 – 1331Proton donor/acceptor
Active sitei161 – 1611Schiff-base intermediate with substrate
Binding sitei203 – 2031Pyruvate; via carbonyl oxygenUniRule annotation2 Publications

GO - Molecular functioni

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

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 lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi44 – 441T → S: 8% of wild-type activity. 4-fold decrease in affinity for pyruvate, but nearly no change in that for (S)-ASA. 2 Publications
Mutagenesisi44 – 441T → V: Reduced kcat by 99.9%. 2 Publications
Mutagenesisi107 – 1071Y → F: Reduced kcat by 90%. 2 Publications
Mutagenesisi107 – 1071Y → 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 Publications
Mutagenesisi133 – 1331Y → F: Reduced kcat by 99.7%. Reduced affinity for both substrates. 1 Publication
Mutagenesisi138 – 1381R → A or H: Strongly increased KM for L-aspartate 4-semialdehyde. No effect on KM for pyruvate. Reduced activity by 99.7%. 1 Publication
Mutagenesisi161 – 1611K → A: 0.1% of wild-type activity. 3-fold decrease in affinity for pyruvate, and 2-fold decrease in that for (S)-ASA. 1 Publication
Mutagenesisi161 – 1611K → R: 0.35% of wild-type activity. 3-fold decrease in affinity for pyruvate, but nearly no change in that for (S)-ASA. 1 Publication
Mutagenesisi197 – 1971L → 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 Publication

Chemistry

ChEMBLiCHEMBL4083.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 2922924-hydroxy-tetrahydrodipicolinate synthasePRO_0000103110Add
BLAST

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: IntAct

Protein-protein interaction databases

IntActiP0A6L2. 3 interactions.
STRINGi511145.b2478.

Chemistry

BindingDBiP0A6L2.

Structurei

Secondary structure

1
292
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi4 – 85Combined sources
Beta strandi17 – 193Combined sources
Helixi21 – 3414Combined sources
Beta strandi38 – 436Combined sources
Turni44 – 474Combined sources
Helixi48 – 503Combined sources
Helixi53 – 6715Combined sources
Beta strandi73 – 764Combined sources
Helixi82 – 9110Combined sources
Turni92 – 943Combined sources
Beta strandi98 – 1036Combined sources
Helixi112 – 12312Combined sources
Beta strandi130 – 1334Combined sources
Helixi136 – 1394Combined sources
Helixi145 – 1528Combined sources
Beta strandi157 – 1604Combined sources
Helixi169 – 1746Combined sources
Beta strandi181 – 1866Combined sources
Helixi188 – 1903Combined sources
Helixi191 – 1966Combined sources
Beta strandi201 – 2055Combined sources
Helixi206 – 2083Combined sources
Helixi211 – 22212Combined sources
Helixi226 – 24217Combined sources
Beta strandi245 – 2473Combined sources
Helixi250 – 2589Combined sources
Beta strandi261 – 2633Combined sources
Helixi276 – 28813Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP0A6L2.
SMRiP0A6L2. Positions 1-292.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti207 – 2071A → T in AAA23665 (PubMed:3514578).Curated
Sequence conflicti224 – 2241G → E in AAA23665 (PubMed:3514578).Curated

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
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[»]
ProteinModelPortaliP0A6L2.
SMRiP0A6L2. Positions 1-292.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP0A6L2. 3 interactions.
STRINGi511145.b2478.

Chemistry

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: September 7, 2016
This is version 106 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.