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Protein

4-hydroxy-tetrahydrodipicolinate synthase

Gene

dapA

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: -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

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

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

Keywordsi

Molecular functionAllosteric enzyme, Lyase
Biological processAmino-acid biosynthesis, Diaminopimelate biosynthesis, Lysine biosynthesis
LigandSchiff base

Enzyme and pathway databases

BioCyciEcoCyc:DIHYDRODIPICSYN-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: EcoCyc

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-2DPAGEiP0A6L2

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

BioGridi426196855 interactors.
IntActiP0A6L2 3 interactors.
STRINGi316385.ECDH10B_2644

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[»]
5T25X-ray1.99A/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
Gene3Di3.20.20.701 hit
HAMAPiMF_00418 DapA, 1 hit
InterProiView protein in InterPro
IPR013785 Aldolase_TIM
IPR005263 DapA
IPR002220 DapA-like
IPR020625 Schiff_base-form_aldolases_AS
IPR020624 Schiff_base-form_aldolases_CS
PANTHERiPTHR12128 PTHR12128, 1 hit
PfamiView protein in Pfam
PF00701 DHDPS, 1 hit
PIRSFiPIRSF001365 DHDPS, 1 hit
PRINTSiPR00146 DHPICSNTHASE
SMARTiView protein in SMART
SM01130 DHDPS, 1 hit
TIGRFAMsiTIGR00674 dapA, 1 hit
PROSITEiView protein in PROSITE
PS00665 DHDPS_1, 1 hit
PS00666 DHDPS_2, 1 hit

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
PATRICifig|1411691.4.peg.4261

Similar proteinsi

Entry informationi

Entry nameiDAPA_ECOLI
AccessioniPrimary (citable) accession number: P0A6L2
Secondary accession number(s): P05640, P78223
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: May 10, 2005
Last modified: April 25, 2018
This is version 120 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

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