DAPA_ECOLI
ID DAPA_ECOLI Reviewed; 292 AA.
AC P0A6L2; P05640; P78223;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=4-hydroxy-tetrahydrodipicolinate synthase {ECO:0000255|HAMAP-Rule:MF_00418};
DE Short=HTPA synthase {ECO:0000255|HAMAP-Rule:MF_00418};
DE EC=4.3.3.7 {ECO:0000255|HAMAP-Rule:MF_00418};
GN Name=dapA {ECO:0000255|HAMAP-Rule:MF_00418};
GN OrderedLocusNames=b2478, JW2463;
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=3514578; DOI=10.1128/jb.166.1.297-300.1986;
RA Richaud F., Richaud C., Ratet P., Patte J.-C.;
RT "Chromosomal location and nucleotide sequence of the Escherichia coli dapA
RT gene.";
RL J. Bacteriol. 166:297-300(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=9205837; DOI=10.1093/dnares/4.2.91;
RA Yamamoto Y., Aiba H., Baba T., Hayashi K., Inada T., Isono K., Itoh T.,
RA Kimura S., Kitagawa M., Makino K., Miki T., Mitsuhashi N., Mizobuchi K.,
RA Mori H., Nakade S., Nakamura Y., Nashimoto H., Oshima T., Oyama S.,
RA Saito N., Sampei G., Satoh Y., Sivasundaram S., Tagami H., Takahashi H.,
RA Takeda J., Takemoto K., Uehara K., Wada C., Yamagata S., Horiuchi T.;
RT "Construction of a contiguous 874-kb sequence of the Escherichia coli-K12
RT genome corresponding to 50.0-68.8 min on the linkage map and analysis of
RT its sequence features.";
RL DNA Res. 4:91-113(1997).
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 PROTEIN SEQUENCE OF 1-11.
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RA Frutiger S., Hughes G.J., Pasquali C., Hochstrasser D.F.;
RL Submitted (FEB-1996) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 1-12.
RC STRAIN=K12 / EMG2;
RX PubMed=9298646; DOI=10.1002/elps.1150180807;
RA Link A.J., Robison K., Church G.M.;
RT "Comparing the predicted and observed properties of proteins encoded in the
RT genome of Escherichia coli K-12.";
RL Electrophoresis 18:1259-1313(1997).
RN [7]
RP PROTEIN SEQUENCE OF 1-4.
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=9600841; DOI=10.1006/jmbi.1998.1726;
RA Wilkins M.R., Gasteiger E., Tonella L., Ou K., Tyler M., Sanchez J.-C.,
RA Gooley A.A., Walsh B.J., Bairoch A., Appel R.D., Williams K.L.,
RA Hochstrasser D.F.;
RT "Protein identification with N and C-terminal sequence tags in proteome
RT projects.";
RL J. Mol. Biol. 278:599-608(1998).
RN [8]
RP PROTEIN SEQUENCE OF 156-167, AND ACTIVE SITE.
RX PubMed=1463470; DOI=10.1042/bj2880691;
RA Laber B., Gomis-Rueth F.-X., Romao M.J., Huber R.;
RT "Escherichia coli dihydrodipicolinate synthase. Identification of the
RT active site and crystallization.";
RL Biochem. J. 288:691-695(1992).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 288-292.
RC STRAIN=K12;
RX PubMed=2120198; DOI=10.1128/jb.172.10.6035-6041.1990;
RA Tiedemann A.A., Demarini D.J., Parker J., Smith J.M.;
RT "DNA sequence of the purC gene encoding 5'-phosphoribosyl-5-aminoimidazole-
RT 4-N-succinocarboxamide synthetase and organization of the dapA-purC region
RT of Escherichia coli K-12.";
RL J. Bacteriol. 172:6035-6041(1990).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 288-292.
RC STRAIN=K12;
RX PubMed=1885529; DOI=10.1128/jb.173.17.5523-5531.1991;
RA Bouvier J., Pugsley A.P., Stragier P.;
RT "A gene for a new lipoprotein in the dapA-purC interval of the Escherichia
RT coli chromosome.";
RL J. Bacteriol. 173:5523-5531(1991).
RN [11]
RP IDENTIFICATION BY 2D-GEL.
RX PubMed=9298644; DOI=10.1002/elps.1150180805;
RA VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C.;
RT "Escherichia coli proteome analysis using the gene-protein database.";
RL Electrophoresis 18:1243-1251(1997).
RN [12]
RP ACTIVITY REGULATION.
RX PubMed=9048556; DOI=10.1021/bi962264x;
RA Karsten W.E.;
RT "Dihydrodipicolinate synthase from Escherichia coli: pH dependent changes
RT in the kinetic mechanism and kinetic mechanism of allosteric inhibition by
RT L-lysine.";
RL Biochemistry 36:1730-1739(1997).
RN [13]
RP ACTIVITY REGULATION, KINETIC PARAMETERS, AND MASS SPECTROMETRY.
RX PubMed=14580236; DOI=10.1042/bj20031389;
RA Dobson R.C., Gerrard J.A., Pearce F.G.;
RT "Dihydrodipicolinate synthase is not inhibited by its substrate, (S)-
RT aspartate beta-semialdehyde.";
RL Biochem. J. 377:757-762(2004).
RN [14]
RP SYNTHETIC INHIBITORS.
RX PubMed=18977662; DOI=10.1016/j.bmc.2008.10.026;
RA Boughton B.A., Griffin M.D., O'Donnell P.A., Dobson R.C., Perugini M.A.,
RA Gerrard J.A., Hutton C.A.;
RT "Irreversible inhibition of dihydrodipicolinate synthase by 4-oxo-
RT heptenedioic acid analogues.";
RL Bioorg. Med. Chem. 16:9975-9983(2008).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION OF HTPA AS REACTION PRODUCT,
RP AND SUBSTRATE SPECIFICITY.
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 [16]
RP SYNTHETIC INHIBITORS.
RX PubMed=22386717; DOI=10.1016/j.bmc.2012.01.045;
RA Boughton B.A., Hor L., Gerrard J.A., Hutton C.A.;
RT "1,3-Phenylene bis(ketoacid) derivatives as inhibitors of Escherichia coli
RT dihydrodipicolinate synthase.";
RL Bioorg. Med. Chem. 20:2419-2426(2012).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=7853400; DOI=10.1006/jmbi.1994.0078;
RA Mirwaldt C., Korndoerfer I., Huber R.;
RT "The crystal structure of dihydrodipicolinate synthase from Escherichia
RT coli at 2.5-A resolution.";
RL J. Mol. Biol. 246:227-239(1995).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP IDENTIFICATION OF HTPA AS REACTION PRODUCT, AND CATALYTIC MECHANISM.
RX PubMed=8993314; DOI=10.1021/bi962272d;
RA Blicking S., Renner C., Laber B., Pohlenz H.-D., Holak T.A., Huber R.;
RT "Reaction mechanism of Escherichia coli dihydrodipicolinate synthase
RT investigated by X-ray crystallography and NMR spectroscopy.";
RL Biochemistry 36:24-33(1997).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF MUTANTS VAL-44; PHE-107 AND
RP PHE-133, KINETIC PARAMETERS, MUTAGENESIS OF THR-44; TYR-107 AND TYR-133,
RP AND REACTION MECHANISM.
RX PubMed=15066435; DOI=10.1016/j.jmb.2004.02.060;
RA Dobson R.C.J., Valegaard K., Gerrard J.A.;
RT "The crystal structure of three site-directed mutants of Escherichia coli
RT dihydrodipicolinate synthase: further evidence for a catalytic triad.";
RL J. Mol. Biol. 338:329-339(2004).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH
RP ALLOSTERIC INHIBITOR (S)-LYSINE, AND SUBUNIT.
RX PubMed=16041077; DOI=10.1107/s0907444905016318;
RA Dobson R.C.J., Griffin M.D.W., Jameson G.B., Gerrard J.A.;
RT "The crystal structures of native and (S)-lysine-bound dihydrodipicolinate
RT synthase from Escherichia coli with improved resolution show new features
RT of biological significance.";
RL Acta Crystallogr. D 61:1116-1124(2005).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF MUTANTS ALA-138 AND HIS-138, AND
RP MUTAGENESIS OF ARG-138.
RX PubMed=16185069; DOI=10.1021/bi051281w;
RA Dobson R.C.J., Devenish S.R.A., Turner L.A., Clifford V.R., Pearce F.G.,
RA Jameson G.B., Gerrard J.A.;
RT "Role of arginine 138 in the catalysis and regulation of Escherichia coli
RT dihydrodipicolinate synthase.";
RL Biochemistry 44:13007-13013(2005).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH LYSINE INHIBITOR.
RA Devenish S.R.A., Dobson R.C.J., Jameson G.B., Gerrard J.A.;
RT "The co-crystallisation of (S)-lysine-bound dihydrodipicolinate synthase
RT from E. coli indicates that domain movements are not responsible for (S)-
RT lysine inhibition.";
RL Submitted (AUG-2005) to the PDB data bank.
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS).
RX PubMed=19052357; DOI=10.1107/s1744309108033654;
RA Devenish S.R., Gerrard J.A., Jameson G.B., Dobson R.C.;
RT "The high-resolution structure of dihydrodipicolinate synthase from
RT Escherichia coli bound to its first substrate, pyruvate.";
RL Acta Crystallogr. F 64:1092-1095(2008).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF MUTANT TRP-107, SUBUNIT, AND
RP MUTAGENESIS OF TYR-107.
RX PubMed=18937497; DOI=10.1021/bi801094t;
RA Pearce F.G., Dobson R.C., Weber A., Lane L.A., McCammon M.G., Squire M.A.,
RA Perugini M.A., Jameson G.B., Robinson C.V., Gerrard J.A.;
RT "Mutating the tight-dimer interface of dihydrodipicolinate synthase
RT disrupts the enzyme quaternary structure: toward a monomeric enzyme.";
RL Biochemistry 47:12108-12117(2008).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF MUTANT TYR-197, SUBUNIT, AND
RP MUTAGENESIS OF LEU-197.
RX PubMed=18556019; DOI=10.1016/j.jmb.2008.05.038;
RA Griffin M.D., Dobson R.C., Pearce F.G., Antonio L., Whitten A.E.,
RA Liew C.K., Mackay J.P., Trewhella J., Jameson G.B., Perugini M.A.,
RA Gerrard J.A.;
RT "Evolution of quaternary structure in a homotetrameric enzyme.";
RL J. Mol. Biol. 380:691-703(2008).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS), ACTIVITY REGULATION, AND MASS
RP SPECTROMETRY.
RX PubMed=18787203; DOI=10.1110/ps.037440.108;
RA Dobson R.C., Griffin M.D., Devenish S.R., Pearce F.G., Hutton C.A.,
RA Gerrard J.A., Jameson G.B., Perugini M.A.;
RT "Conserved main-chain peptide distortions: a proposed role for Ile203 in
RT catalysis by dihydrodipicolinate synthase.";
RL Protein Sci. 17:2080-2090(2008).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF MUTANT SER-44, MUTAGENESIS OF
RP THR-44, ACTIVE SITES, AND REACTION MECHANISM.
RX PubMed=19505526; DOI=10.1016/j.biochi.2009.05.013;
RA Dobson R.C., Perugini M.A., Jameson G.B., Gerrard J.A.;
RT "Specificity versus catalytic potency: The role of threonine 44 in
RT Escherichia coli dihydrodipicolinate synthase mediated catalysis.";
RL Biochimie 91:1036-1044(2009).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF MUTANTS ALA-161 AND ARG-161 OF
RP NATIVE PROTEIN AND IN COMPLEX WITH PYRUVATE, AND MUTAGENESIS OF LYS-161.
RX PubMed=20353808; DOI=10.1016/j.biochi.2010.03.004;
RA Soares da Costa T.P., Muscroft-Taylor A.C., Dobson R.C., Devenish S.R.,
RA Jameson G.B., Gerrard J.A.;
RT "How essential is the 'essential' active-site lysine in dihydrodipicolinate
RT synthase?";
RL Biochimie 92:837-845(2010).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH PYRUVATE AND
RP SUBSTRATE ANALOG INHIBITOR.
RX PubMed=22552955; DOI=10.1002/prot.24106;
RA Boughton B.A., Dobson R.C., Hutton C.A.;
RT "The crystal structure of dihydrodipicolinate synthase from Escherichia
RT coli with bound pyruvate and succinic acid semialdehyde: unambiguous
RT resolution of the stereochemistry of the condensation product.";
RL Proteins 80:2117-2122(2012).
CC -!- FUNCTION: Catalyzes the condensation of (S)-aspartate-beta-semialdehyde
CC [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).
CC {ECO:0000255|HAMAP-Rule:MF_00418, ECO:0000269|PubMed:20503968,
CC ECO:0000269|PubMed:8993314}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-aspartate 4-semialdehyde + pyruvate = (2S,4S)-4-hydroxy-
CC 2,3,4,5-tetrahydrodipicolinate + H(+) + H2O; Xref=Rhea:RHEA:34171,
CC ChEBI:CHEBI:15361, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:67139, ChEBI:CHEBI:537519; EC=4.3.3.7;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00418,
CC ECO:0000269|PubMed:20503968, ECO:0000269|PubMed:8993314};
CC -!- ACTIVITY REGULATION: Is allosterically regulated by the feedback
CC inhibitor (S)-lysine. Is inhibited by pyruvate analogs such as 3-
CC fluoropyruvate, 2-ketobutyrate, glyoxylate, and beta-hydroxypyruvate.
CC Is not inhibited by its substrate, (S)-ASA.
CC {ECO:0000269|PubMed:14580236, ECO:0000269|PubMed:18787203,
CC ECO:0000269|PubMed:9048556}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.26 mM for pyruvate {ECO:0000269|PubMed:14580236,
CC ECO:0000269|PubMed:15066435};
CC KM=0.11 mM for L-aspartate-4-semialdehyde
CC {ECO:0000269|PubMed:14580236, ECO:0000269|PubMed:15066435};
CC Vmax=0.58 umol/sec/mg enzyme {ECO:0000269|PubMed:14580236,
CC ECO:0000269|PubMed:15066435};
CC Note=kcat is 124 sec(-1).;
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via DAP
CC pathway; (S)-tetrahydrodipicolinate from L-aspartate: step 3/4.
CC {ECO:0000255|HAMAP-Rule:MF_00418}.
CC -!- SUBUNIT: Homotetramer; dimer of dimers. {ECO:0000255|HAMAP-
CC Rule:MF_00418, ECO:0000269|PubMed:16041077,
CC ECO:0000269|PubMed:18556019, ECO:0000269|PubMed:18937497,
CC ECO:0000269|PubMed:20353808, ECO:0000269|PubMed:22552955,
CC ECO:0000269|Ref.22}.
CC -!- INTERACTION:
CC P0A6L2; P0A6L2: dapA; NbExp=2; IntAct=EBI-907527, EBI-907527;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- MASS SPECTROMETRY: Mass=31272; Mass_error=1; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:14580236};
CC -!- MASS SPECTROMETRY: Mass=31270; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:18787203};
CC -!- SIMILARITY: Belongs to the DapA family. {ECO:0000255|HAMAP-
CC Rule:MF_00418}.
CC -!- CAUTION: Was originally thought to be a dihydrodipicolinate synthase
CC (DHDPS), catalyzing the condensation of (S)-aspartate-beta-semialdehyde
CC [(S)-ASA] and pyruvate to dihydrodipicolinate (DHDP). However, it was
CC shown that the product of the enzymatic reaction is not
CC dihydrodipicolinate but in fact (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-
CC dipicolinic acid (HTPA), and that the consecutive dehydration reaction
CC leading to DHDP is not spontaneous but catalyzed by DapB
CC (PubMed:8993314, PubMed:20503968). {ECO:0000305|PubMed:20503968,
CC ECO:0000305|PubMed:8993314}.
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DR EMBL; M12844; AAA23665.1; -; Genomic_DNA.
DR EMBL; U00096; AAC75531.1; -; Genomic_DNA.
DR EMBL; AP009048; BAA16355.1; -; Genomic_DNA.
DR EMBL; M33928; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X57402; CAA40660.1; -; Genomic_DNA.
DR PIR; E65023; SYECDP.
DR RefSeq; NP_416973.1; NC_000913.3.
DR RefSeq; WP_001311023.1; NZ_LN832404.1.
DR PDB; 1DHP; X-ray; 2.30 A; A/B=1-292.
DR PDB; 1S5T; X-ray; 2.30 A; A/B=1-292.
DR PDB; 1S5V; X-ray; 2.35 A; A/B=1-292.
DR PDB; 1S5W; X-ray; 2.32 A; A/B=1-292.
DR PDB; 1YXC; X-ray; 1.90 A; A/B=1-292.
DR PDB; 1YXD; X-ray; 2.00 A; A/B=1-292.
DR PDB; 2A6L; X-ray; 2.05 A; A/B=1-292.
DR PDB; 2A6N; X-ray; 1.94 A; A/B=1-292.
DR PDB; 2ATS; X-ray; 1.90 A; A/B=1-292.
DR PDB; 2OJP; X-ray; 1.70 A; A/B=1-292.
DR PDB; 2PUR; X-ray; 1.70 A; A/B=1-292.
DR PDB; 3C0J; X-ray; 2.40 A; A/B=1-292.
DR PDB; 3DEN; X-ray; 2.20 A; A/B=1-292.
DR PDB; 3DU0; X-ray; 2.00 A; A/B=1-292.
DR PDB; 3I7Q; X-ray; 2.00 A; A/B=1-292.
DR PDB; 3I7R; X-ray; 2.10 A; A/B=1-292.
DR PDB; 3I7S; X-ray; 2.30 A; A/B=1-292.
DR PDB; 4EOU; X-ray; 2.30 A; A/B=1-292.
DR PDB; 5T25; X-ray; 1.99 A; A/B=1-292.
DR PDB; 5T26; X-ray; 2.10 A; A/B=1-292.
DR PDBsum; 1DHP; -.
DR PDBsum; 1S5T; -.
DR PDBsum; 1S5V; -.
DR PDBsum; 1S5W; -.
DR PDBsum; 1YXC; -.
DR PDBsum; 1YXD; -.
DR PDBsum; 2A6L; -.
DR PDBsum; 2A6N; -.
DR PDBsum; 2ATS; -.
DR PDBsum; 2OJP; -.
DR PDBsum; 2PUR; -.
DR PDBsum; 3C0J; -.
DR PDBsum; 3DEN; -.
DR PDBsum; 3DU0; -.
DR PDBsum; 3I7Q; -.
DR PDBsum; 3I7R; -.
DR PDBsum; 3I7S; -.
DR PDBsum; 4EOU; -.
DR PDBsum; 5T25; -.
DR PDBsum; 5T26; -.
DR AlphaFoldDB; P0A6L2; -.
DR SMR; P0A6L2; -.
DR BioGRID; 4261968; 55.
DR BioGRID; 851291; 1.
DR IntAct; P0A6L2; 3.
DR STRING; 511145.b2478; -.
DR BindingDB; P0A6L2; -.
DR ChEMBL; CHEMBL4083; -.
DR SWISS-2DPAGE; P0A6L2; -.
DR jPOST; P0A6L2; -.
DR PaxDb; P0A6L2; -.
DR PRIDE; P0A6L2; -.
DR EnsemblBacteria; AAC75531; AAC75531; b2478.
DR EnsemblBacteria; BAA16355; BAA16355; BAA16355.
DR GeneID; 58388531; -.
DR GeneID; 946952; -.
DR KEGG; ecj:JW2463; -.
DR KEGG; eco:b2478; -.
DR PATRIC; fig|1411691.4.peg.4261; -.
DR EchoBASE; EB0201; -.
DR eggNOG; COG0329; Bacteria.
DR HOGENOM; CLU_049343_7_1_6; -.
DR InParanoid; P0A6L2; -.
DR OMA; GMDACVP; -.
DR PhylomeDB; P0A6L2; -.
DR BioCyc; EcoCyc:DIHYDRODIPICSYN-MON; -.
DR BioCyc; MetaCyc:DIHYDRODIPICSYN-MON; -.
DR BRENDA; 4.3.3.7; 2026.
DR SABIO-RK; P0A6L2; -.
DR UniPathway; UPA00034; UER00017.
DR EvolutionaryTrace; P0A6L2; -.
DR PRO; PR:P0A6L2; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0008840; F:4-hydroxy-tetrahydrodipicolinate synthase activity; IDA:EcoCyc.
DR GO; GO:0042802; F:identical protein binding; IDA:EcoCyc.
DR GO; GO:0019877; P:diaminopimelate biosynthetic process; IDA:EcoliWiki.
DR GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IEA:UniProtKB-UniPathway.
DR CDD; cd00950; DHDPS; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR HAMAP; MF_00418; DapA; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR005263; DapA.
DR InterPro; IPR002220; DapA-like.
DR InterPro; IPR020625; Schiff_base-form_aldolases_AS.
DR InterPro; IPR020624; Schiff_base-form_aldolases_CS.
DR PANTHER; PTHR12128; PTHR12128; 1.
DR Pfam; PF00701; DHDPS; 1.
DR PIRSF; PIRSF001365; DHDPS; 1.
DR PRINTS; PR00146; DHPICSNTHASE.
DR SMART; SM01130; DHDPS; 1.
DR TIGRFAMs; TIGR00674; dapA; 1.
DR PROSITE; PS00665; DHDPS_1; 1.
DR PROSITE; PS00666; DHDPS_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; Amino-acid biosynthesis; Cytoplasm;
KW Diaminopimelate biosynthesis; Direct protein sequencing; Lyase;
KW Lysine biosynthesis; Reference proteome; Schiff base.
FT CHAIN 1..292
FT /note="4-hydroxy-tetrahydrodipicolinate synthase"
FT /id="PRO_0000103110"
FT ACT_SITE 133
FT /note="Proton donor/acceptor"
FT ACT_SITE 161
FT /note="Schiff-base intermediate with substrate"
FT BINDING 45
FT /ligand="pyruvate"
FT /ligand_id="ChEBI:CHEBI:15361"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00418,
FT ECO:0000269|PubMed:20353808, ECO:0000269|PubMed:22552955"
FT BINDING 203
FT /ligand="pyruvate"
FT /ligand_id="ChEBI:CHEBI:15361"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00418,
FT ECO:0000269|PubMed:20353808, ECO:0000269|PubMed:22552955"
FT SITE 44
FT /note="Part of a proton relay during catalysis"
FT SITE 49
FT /note="L-lysine inhibitor binding; via carbonyl oxygen"
FT SITE 80
FT /note="L-lysine inhibitor binding"
FT SITE 84
FT /note="L-lysine inhibitor binding"
FT SITE 106
FT /note="L-lysine inhibitor binding"
FT SITE 107
FT /note="Part of a proton relay during catalysis"
FT MUTAGEN 44
FT /note="T->S: 8% of wild-type activity. 4-fold decrease in
FT affinity for pyruvate, but nearly no change in that for
FT (S)-ASA."
FT /evidence="ECO:0000269|PubMed:15066435,
FT ECO:0000269|PubMed:19505526"
FT MUTAGEN 44
FT /note="T->V: Reduced kcat by 99.9%."
FT /evidence="ECO:0000269|PubMed:15066435,
FT ECO:0000269|PubMed:19505526"
FT MUTAGEN 107
FT /note="Y->F: Reduced kcat by 90%."
FT /evidence="ECO:0000269|PubMed:15066435,
FT ECO:0000269|PubMed:18937497"
FT MUTAGEN 107
FT /note="Y->W: Reduced activity by 95%. Reduced affinity for
FT both substrates. Exists as a mixture of monomer, dimer and
FT tetramer in solution. Has significantly lower thermal
FT stability than the wild-type enzyme."
FT /evidence="ECO:0000269|PubMed:15066435,
FT ECO:0000269|PubMed:18937497"
FT MUTAGEN 133
FT /note="Y->F: Reduced kcat by 99.7%. Reduced affinity for
FT both substrates."
FT /evidence="ECO:0000269|PubMed:15066435"
FT MUTAGEN 138
FT /note="R->A,H: Strongly increased KM for L-aspartate 4-
FT semialdehyde. No effect on KM for pyruvate. Reduced
FT activity by 99.7%."
FT /evidence="ECO:0000269|PubMed:16185069"
FT MUTAGEN 161
FT /note="K->A: 0.1% of wild-type activity. 3-fold decrease in
FT affinity for pyruvate, and 2-fold decrease in that for (S)-
FT ASA."
FT /evidence="ECO:0000269|PubMed:20353808"
FT MUTAGEN 161
FT /note="K->R: 0.35% of wild-type activity. 3-fold decrease
FT in affinity for pyruvate, but nearly no change in that for
FT (S)-ASA."
FT /evidence="ECO:0000269|PubMed:20353808"
FT MUTAGEN 197
FT /note="L->Y,D: 1.4 to 2.5% of wild-type activity. Decrease
FT in affinity for pyruvate, but nearly no change in that for
FT (S)-ASA. Exists as a dimer in solution."
FT /evidence="ECO:0000269|PubMed:18556019"
FT CONFLICT 207
FT /note="A -> T (in Ref. 1; AAA23665)"
FT /evidence="ECO:0000305"
FT CONFLICT 224
FT /note="G -> E (in Ref. 1; AAA23665)"
FT /evidence="ECO:0000305"
FT STRAND 4..8
FT /evidence="ECO:0007829|PDB:2OJP"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:2PUR"
FT HELIX 21..34
FT /evidence="ECO:0007829|PDB:2OJP"
FT STRAND 38..43
FT /evidence="ECO:0007829|PDB:2OJP"
FT TURN 44..47
FT /evidence="ECO:0007829|PDB:2OJP"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:2OJP"
FT HELIX 53..67
FT /evidence="ECO:0007829|PDB:2OJP"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:2OJP"
FT HELIX 82..91
FT /evidence="ECO:0007829|PDB:2OJP"
FT TURN 92..94
FT /evidence="ECO:0007829|PDB:2OJP"
FT STRAND 98..103
FT /evidence="ECO:0007829|PDB:2OJP"
FT HELIX 112..123
FT /evidence="ECO:0007829|PDB:2OJP"
FT STRAND 130..133
FT /evidence="ECO:0007829|PDB:2OJP"
FT HELIX 136..139
FT /evidence="ECO:0007829|PDB:2OJP"
FT HELIX 145..152
FT /evidence="ECO:0007829|PDB:2OJP"
FT STRAND 157..160
FT /evidence="ECO:0007829|PDB:2OJP"
FT HELIX 169..174
FT /evidence="ECO:0007829|PDB:2OJP"
FT STRAND 181..186
FT /evidence="ECO:0007829|PDB:2OJP"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:2OJP"
FT HELIX 191..196
FT /evidence="ECO:0007829|PDB:2OJP"
FT STRAND 201..205
FT /evidence="ECO:0007829|PDB:2OJP"
FT HELIX 206..208
FT /evidence="ECO:0007829|PDB:2OJP"
FT HELIX 211..222
FT /evidence="ECO:0007829|PDB:2OJP"
FT HELIX 226..242
FT /evidence="ECO:0007829|PDB:2OJP"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:2OJP"
FT HELIX 250..258
FT /evidence="ECO:0007829|PDB:2OJP"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:2OJP"
FT HELIX 276..288
FT /evidence="ECO:0007829|PDB:2OJP"
SQ SEQUENCE 292 AA; 31270 MW; 3970543296A77C08 CRC64;
MFTGSIVAIV TPMDEKGNVC RASLKKLIDY HVASGTSAIV SVGTTGESAT LNHDEHADVV
MMTLDLADGR IPVIAGTGAN ATAEAISLTQ RFNDSGIVGC LTVTPYYNRP SQEGLYQHFK
AIAEHTDLPQ ILYNVPSRTG CDLLPETVGR LAKVKNIIGI KEATGNLTRV NQIKELVSDD
FVLLSGDDAS ALDFMQLGGH GVISVTANVA ARDMAQMCKL AAEGHFAEAR VINQRLMPLH
NKLFVEPNPI PVKWACKELG LVATDTLRLP MTPITDSGRE TVRAALKHAG LL
