DAPA_THEMA
ID DAPA_THEMA Reviewed; 294 AA.
AC Q9X1K9;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, 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}; OrderedLocusNames=TM_1521;
OS Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826
OS / MSB8).
OC Bacteria; Thermotogae; Thermotogales; Thermotogaceae; Thermotoga.
OX NCBI_TaxID=243274;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8;
RX PubMed=10360571; DOI=10.1038/20601;
RA Nelson K.E., Clayton R.A., Gill S.R., Gwinn M.L., Dodson R.J., Haft D.H.,
RA Hickey E.K., Peterson J.D., Nelson W.C., Ketchum K.A., McDonald L.A.,
RA Utterback T.R., Malek J.A., Linher K.D., Garrett M.M., Stewart A.M.,
RA Cotton M.D., Pratt M.S., Phillips C.A., Richardson D.L., Heidelberg J.F.,
RA Sutton G.G., Fleischmann R.D., Eisen J.A., White O., Salzberg S.L.,
RA Smith H.O., Venter J.C., Fraser C.M.;
RT "Evidence for lateral gene transfer between Archaea and Bacteria from
RT genome sequence of Thermotoga maritima.";
RL Nature 399:323-329(1999).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS), FUNCTION, BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVITY REGULATION, AND SUBUNIT.
RC STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8;
RX PubMed=16872276; DOI=10.1042/bj20060771;
RA Pearce F.G., Perugini M.A., McKerchar H.J., Gerrard J.A.;
RT "Dihydrodipicolinate synthase from Thermotoga maritima.";
RL Biochem. J. 400:359-366(2006).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF MUTANT ALA-166/ALA-167/ALA-168 AND
RP MUTANT ALA-233/ALA-237, MUTAGENESIS OF 166-ASP--ASP-168, KINETIC
RP PARAMETERS, AND SUBUNIT.
RC STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8;
RX PubMed=21803176; DOI=10.1016/j.bbapap.2011.07.016;
RA Pearce F.G., Dobson R.C., Jameson G.B., Perugini M.A., Gerrard J.A.;
RT "Characterization of monomeric dihydrodipicolinate synthase variant reveals
RT the importance of substrate binding in optimizing oligomerization.";
RL Biochim. Biophys. Acta 1814:1900-1909(2011).
CC -!- FUNCTION: Catalyzes the condensation of (S)-aspartate-beta-semialdehyde
CC [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).
CC {ECO:0000305|PubMed:16872276}.
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 -!- ACTIVITY REGULATION: Is not inhibited by (S)-lysine, in contrast to
CC E.coli DapA. {ECO:0000269|PubMed:16872276}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.053 mM for pyruvate (at 30 degrees Celsius)
CC {ECO:0000269|PubMed:16872276};
CC KM=0.08 mM for pyruvate (at 30 degrees Celsius)
CC {ECO:0000269|PubMed:21803176};
CC KM=0.15 mM for pyruvate (at 45 degrees Celsius)
CC {ECO:0000269|PubMed:21803176};
CC KM=0.16 mM for L-aspartate-4-semialdehyde (at 30 degrees Celsius)
CC {ECO:0000269|PubMed:16872276};
CC KM=0.23 mM for L-aspartate-4-semialdehyde (at 30 degrees Celsius)
CC {ECO:0000269|PubMed:21803176};
CC KM=0.36 mM for L-aspartate-4-semialdehyde (at 45 degrees Celsius)
CC {ECO:0000269|PubMed:21803176};
CC Vmax=1.01 umol/sec/mg enzyme (at 30 degrees Celsius)
CC {ECO:0000269|PubMed:16872276};
CC Note=kcat is 136 sec(-1) and 465 sec (-1) at 30 and 45 degrees
CC Celsius, respectively. {ECO:0000269|PubMed:21803176};
CC Temperature dependence:
CC Highly thermostable. Retains over 60% of the activity after 7 hours
CC incubation at 90 degrees Celsius. {ECO:0000269|PubMed:16872276};
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:16872276,
CC ECO:0000269|PubMed:21803176}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00418}.
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 in E.coli 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 {ECO:0000305}.
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DR EMBL; AE000512; AAD36588.1; -; Genomic_DNA.
DR PIR; B72246; B72246.
DR RefSeq; NP_229321.1; NC_000853.1.
DR RefSeq; WP_004081879.1; NZ_CP011107.1.
DR PDB; 1O5K; X-ray; 1.80 A; A/B=1-294.
DR PDB; 3PB0; X-ray; 2.00 A; A/B/C/D=1-294.
DR PDB; 3PB2; X-ray; 1.90 A; A/B/C/D/E/F=1-294.
DR PDBsum; 1O5K; -.
DR PDBsum; 3PB0; -.
DR PDBsum; 3PB2; -.
DR AlphaFoldDB; Q9X1K9; -.
DR SMR; Q9X1K9; -.
DR STRING; 243274.THEMA_06695; -.
DR DrugBank; DB02370; Nz-(1-Carboxyethyl)-Lysine.
DR EnsemblBacteria; AAD36588; AAD36588; TM_1521.
DR KEGG; tma:TM1521; -.
DR eggNOG; COG0329; Bacteria.
DR InParanoid; Q9X1K9; -.
DR OMA; GMDACVP; -.
DR OrthoDB; 1438588at2; -.
DR BRENDA; 4.3.3.7; 6331.
DR UniPathway; UPA00034; UER00017.
DR EvolutionaryTrace; Q9X1K9; -.
DR Proteomes; UP000008183; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0008840; F:4-hydroxy-tetrahydrodipicolinate synthase activity; IBA:GO_Central.
DR GO; GO:0019877; P:diaminopimelate biosynthetic process; IEA:UniProtKB-UniRule.
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; Amino-acid biosynthesis; Cytoplasm;
KW Diaminopimelate biosynthesis; Lyase; Lysine biosynthesis;
KW Reference proteome; Schiff base.
FT CHAIN 1..294
FT /note="4-hydroxy-tetrahydrodipicolinate synthase"
FT /id="PRO_0000103175"
FT ACT_SITE 132
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00418"
FT ACT_SITE 161
FT /note="Schiff-base intermediate with substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00418"
FT BINDING 44
FT /ligand="pyruvate"
FT /ligand_id="ChEBI:CHEBI:15361"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00418"
FT BINDING 206
FT /ligand="pyruvate"
FT /ligand_id="ChEBI:CHEBI:15361"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00418"
FT SITE 43
FT /note="Part of a proton relay during catalysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00418"
FT SITE 106
FT /note="Part of a proton relay during catalysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00418"
FT MUTAGEN 166..168
FT /note="DID->AAA: Exists as a monomer in solution. Decreased
FT activity and substrate affinity. Reduced thermal
FT stability."
FT /evidence="ECO:0000269|PubMed:21803176"
FT STRAND 3..8
FT /evidence="ECO:0007829|PDB:1O5K"
FT HELIX 20..32
FT /evidence="ECO:0007829|PDB:1O5K"
FT STRAND 37..42
FT /evidence="ECO:0007829|PDB:1O5K"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:1O5K"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:1O5K"
FT HELIX 52..66
FT /evidence="ECO:0007829|PDB:1O5K"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:1O5K"
FT HELIX 81..94
FT /evidence="ECO:0007829|PDB:1O5K"
FT STRAND 97..102
FT /evidence="ECO:0007829|PDB:1O5K"
FT HELIX 111..122
FT /evidence="ECO:0007829|PDB:1O5K"
FT STRAND 129..133
FT /evidence="ECO:0007829|PDB:1O5K"
FT HELIX 135..138
FT /evidence="ECO:0007829|PDB:1O5K"
FT HELIX 144..153
FT /evidence="ECO:0007829|PDB:1O5K"
FT STRAND 157..162
FT /evidence="ECO:0007829|PDB:1O5K"
FT HELIX 167..180
FT /evidence="ECO:0007829|PDB:1O5K"
FT STRAND 185..190
FT /evidence="ECO:0007829|PDB:1O5K"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:1O5K"
FT HELIX 194..200
FT /evidence="ECO:0007829|PDB:1O5K"
FT STRAND 204..208
FT /evidence="ECO:0007829|PDB:1O5K"
FT HELIX 209..211
FT /evidence="ECO:0007829|PDB:1O5K"
FT HELIX 214..225
FT /evidence="ECO:0007829|PDB:1O5K"
FT HELIX 229..245
FT /evidence="ECO:0007829|PDB:1O5K"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:1O5K"
FT HELIX 253..261
FT /evidence="ECO:0007829|PDB:1O5K"
FT HELIX 278..290
FT /evidence="ECO:0007829|PDB:1O5K"
SQ SEQUENCE 294 AA; 32390 MW; 64C93C64734A351D CRC64;
MFRGVGTAIV TPFKNGELDL ESYERLVRYQ LENGVNALIV LGTTGESPTV NEDEREKLVS
RTLEIVDGKI PVIVGAGTNS TEKTLKLVKQ AEKLGANGVL VVTPYYNKPT QEGLYQHYKY
ISERTDLGIV VYNVPGRTGV NVLPETAARI AADLKNVVGI KEANPDIDQI DRTVSLTKQA
RSDFMVWSGN DDRTFYLLCA GGDGVISVVS NVAPKQMVEL CAEYFSGNLE KSREVHRKLR
PLMKALFVET NPIPVKAALN LMGFIENELR LPLVPASEKT VELLRNVLKE SGLL
