P0A6L2 · DAPA_ECOLI
- Protein4-hydroxy-tetrahydrodipicolinate synthase
- GenedapA
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids292 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).
Catalytic activity
- L-aspartate 4-semialdehyde + pyruvate = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H+ + H2O
Activity regulation
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.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.26 mM | pyruvate | |||||
0.11 mM | L-aspartate-4-semialdehyde |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
0.58 μmol/sec/mg |
kcat is 124 sec-1.
Pathway
Amino-acid biosynthesis; L-lysine biosynthesis via DAP pathway; (S)-tetrahydrodipicolinate from L-aspartate: step 3/4.
Features
Showing features for site, binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 44 | Part of a proton relay during catalysis | ||||
Sequence: T | ||||||
Binding site | 45 | pyruvate (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Site | 49 | L-lysine inhibitor binding; via carbonyl oxygen | ||||
Sequence: A | ||||||
Site | 80 | L-lysine inhibitor binding | ||||
Sequence: N | ||||||
Site | 84 | L-lysine inhibitor binding | ||||
Sequence: E | ||||||
Site | 106 | L-lysine inhibitor binding | ||||
Sequence: Y | ||||||
Site | 107 | Part of a proton relay during catalysis | ||||
Sequence: Y | ||||||
Active site | 133 | Proton donor/acceptor | ||||
Sequence: Y | ||||||
Active site | 161 | Schiff-base intermediate with substrate | ||||
Sequence: K | ||||||
Binding site | 203 | pyruvate (UniProtKB | ChEBI) | ||||
Sequence: I |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Molecular Function | 4-hydroxy-tetrahydrodipicolinate synthase activity | |
Molecular Function | identical protein binding | |
Biological Process | diaminopimelate biosynthetic process | |
Biological Process | lysine biosynthetic process via diaminopimelate |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended name4-hydroxy-tetrahydrodipicolinate synthase
- EC number
- Short namesHTPA synthase
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageBacteria > Pseudomonadota > Gammaproteobacteria > Enterobacterales > Enterobacteriaceae > Escherichia
Accessions
- Primary accessionP0A6L2
- Secondary accessions
Proteomes
Subcellular Location
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 44 | 8% of wild-type activity. 4-fold decrease in affinity for pyruvate, but nearly no change in that for (S)-ASA. | ||||
Sequence: T → S | ||||||
Mutagenesis | 44 | Reduced kcat by 99.9%. | ||||
Sequence: T → V | ||||||
Mutagenesis | 107 | Reduced kcat by 90%. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 107 | 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. | ||||
Sequence: Y → W | ||||||
Mutagenesis | 133 | Reduced kcat by 99.7%. Reduced affinity for both substrates. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 138 | Strongly increased KM for L-aspartate 4-semialdehyde. No effect on KM for pyruvate. Reduced activity by 99.7%. | ||||
Sequence: R → A or H | ||||||
Mutagenesis | 161 | 0.1% of wild-type activity. 3-fold decrease in affinity for pyruvate, and 2-fold decrease in that for (S)-ASA. | ||||
Sequence: K → A | ||||||
Mutagenesis | 161 | 0.35% of wild-type activity. 3-fold decrease in affinity for pyruvate, but nearly no change in that for (S)-ASA. | ||||
Sequence: K → R | ||||||
Mutagenesis | 197 | 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. | ||||
Sequence: L → Y or D |
Chemistry
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000103110 | 1-292 | 4-hydroxy-tetrahydrodipicolinate synthase | |||
Sequence: MFTGSIVAIVTPMDEKGNVCRASLKKLIDYHVASGTSAIVSVGTTGESATLNHDEHADVVMMTLDLADGRIPVIAGTGANATAEAISLTQRFNDSGIVGCLTVTPYYNRPSQEGLYQHFKAIAEHTDLPQILYNVPSRTGCDLLPETVGRLAKVKNIIGIKEATGNLTRVNQIKELVSDDFVLLSGDDASALDFMQLGGHGVISVTANVAARDMAQMCKLAAEGHFAEARVINQRLMPLHNKLFVEPNPIPVKWACKELGLVATDTLRLPMTPITDSGRETVRAALKHAGLL |
Proteomic databases
Interaction
Subunit
Homotetramer; dimer of dimers.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P0A6L2 | dapA P0A6L2 | 2 | EBI-907527, EBI-907527 |
Protein-protein interaction databases
Chemistry
Structure
Sequence
- Sequence statusComplete
- Length292
- Mass (Da)31,270
- Last updated2005-05-10 v1
- Checksum3970543296A77C08
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 207 | in Ref. 1; AAA23665 | ||||
Sequence: A → T | ||||||
Sequence conflict | 224 | in Ref. 1; AAA23665 | ||||
Sequence: G → E |
Mass Spectrometry
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M12844 EMBL· GenBank· DDBJ | AAA23665.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U00096 EMBL· GenBank· DDBJ | AAC75531.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AP009048 EMBL· GenBank· DDBJ | BAA16355.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M33928 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
X57402 EMBL· GenBank· DDBJ | CAA40660.1 EMBL· GenBank· DDBJ | Genomic DNA |