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 27-MAR-2024, entry version 151. 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; Pseudomonadota; 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- CC hydroxy-2,3,4,5-tetrahydrodipicolinate + H(+) + H2O; CC Xref=Rhea:RHEA:34171, ChEBI:CHEBI:15361, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7JZ7; X-ray; 1.74 A; A/B=1-292. DR PDB; 7JZ8; X-ray; 1.82 A; A/B=1-292. DR PDB; 7JZ9; X-ray; 1.82 A; A/B=1-292. DR PDB; 7JZA; X-ray; 1.82 A; A/B=1-292. DR PDB; 7JZB; X-ray; 1.93 A; A/B=1-292. DR PDB; 7JZC; X-ray; 2.07 A; A/B=1-292. DR PDB; 7JZD; X-ray; 1.91 A; A/B=1-292. DR PDB; 7JZE; X-ray; 2.00 A; A/B=1-292. DR PDB; 7JZF; X-ray; 1.82 A; A/B=1-292. DR PDB; 7JZG; X-ray; 1.82 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 PDBsum; 7JZ7; -. DR PDBsum; 7JZ8; -. DR PDBsum; 7JZ9; -. DR PDBsum; 7JZA; -. DR PDBsum; 7JZB; -. DR PDBsum; 7JZC; -. DR PDBsum; 7JZD; -. DR PDBsum; 7JZE; -. DR PDBsum; 7JZF; -. DR PDBsum; 7JZG; -. 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 jPOST; P0A6L2; -. DR PaxDb; 511145-b2478; -. DR EnsemblBacteria; AAC75531; AAC75531; b2478. 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 OrthoDB; 9782828at2; -. DR PhylomeDB; P0A6L2; -. DR BioCyc; EcoCyc:DIHYDRODIPICSYN-MONOMER; -. DR BioCyc; MetaCyc:DIHYDRODIPICSYN-MONOMER; -. 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; Aldolase class I; 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 NCBIfam; TIGR00674; dapA; 1. DR PANTHER; PTHR12128:SF72; 4-HYDROXY-2-OXOGLUTARATE ALDOLASE, MITOCHONDRIAL; 1. DR PANTHER; PTHR12128; DIHYDRODIPICOLINATE SYNTHASE; 1. DR Pfam; PF00701; DHDPS; 1. DR PIRSF; PIRSF001365; DHDPS; 1. DR PRINTS; PR00146; DHPICSNTHASE. DR SMART; SM01130; DHDPS; 1. DR SUPFAM; SSF51569; Aldolase; 1. DR PROSITE; PS00665; DHDPS_1; 1. DR PROSITE; PS00666; DHDPS_2; 1. DR SWISS-2DPAGE; P0A6L2; -. 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 FT 4-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 FT (S)-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 //