DAPA_NEIMB
ID DAPA_NEIMB Reviewed; 291 AA.
AC Q9JZR4;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 124.
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=NMB0929;
OS Neisseria meningitidis serogroup B (strain MC58).
OC Bacteria; Proteobacteria; Betaproteobacteria; Neisseriales; Neisseriaceae;
OC Neisseria.
OX NCBI_TaxID=122586;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MC58;
RX PubMed=10710307; DOI=10.1126/science.287.5459.1809;
RA Tettelin H., Saunders N.J., Heidelberg J.F., Jeffries A.C., Nelson K.E.,
RA Eisen J.A., Ketchum K.A., Hood D.W., Peden J.F., Dodson R.J., Nelson W.C.,
RA Gwinn M.L., DeBoy R.T., Peterson J.D., Hickey E.K., Haft D.H.,
RA Salzberg S.L., White O., Fleischmann R.D., Dougherty B.A., Mason T.M.,
RA Ciecko A., Parksey D.S., Blair E., Cittone H., Clark E.B., Cotton M.D.,
RA Utterback T.R., Khouri H.M., Qin H., Vamathevan J.J., Gill J., Scarlato V.,
RA Masignani V., Pizza M., Grandi G., Sun L., Smith H.O., Fraser C.M.,
RA Moxon E.R., Rappuoli R., Venter J.C.;
RT "Complete genome sequence of Neisseria meningitidis serogroup B strain
RT MC58.";
RL Science 287:1809-1815(2000).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), FUNCTION, KINETIC PARAMETERS,
RP ACTIVITY REGULATION, IDENTIFICATION BY MASS SPECTROMETRY, AND SUBUNIT.
RC STRAIN=MC58;
RX PubMed=19236959; DOI=10.1016/j.bbapap.2009.02.003;
RA Devenish S.R., Huisman F.H., Parker E.J., Hadfield A.T., Gerrard J.A.;
RT "Cloning and characterisation of dihydrodipicolinate synthase from the
RT pathogen Neisseria meningitidis.";
RL Biochim. Biophys. Acta 1794:1168-1174(2009).
CC -!- FUNCTION: Catalyzes the condensation of (S)-aspartate-beta-semialdehyde
CC [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).
CC {ECO:0000305|PubMed:19236959}.
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 allosterically feedback inhibited by lysine;
CC the N.meningitidis enzyme is significantly more sensitive to lysine
CC than the E.coli enzyme. Shows substrate inhibition by (S)-ASA, with a
CC Ki of 1.7 mM. {ECO:0000269|PubMed:19236959}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.50 mM for pyruvate {ECO:0000269|PubMed:19236959};
CC KM=0.052 mM for L-aspartate-4-semialdehyde
CC {ECO:0000269|PubMed:19236959};
CC Note=kcat is 46.7 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. {ECO:0000269|PubMed:19236959}.
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; AE002098; AAF41336.1; -; Genomic_DNA.
DR PIR; D81141; D81141.
DR RefSeq; NP_273968.1; NC_003112.2.
DR RefSeq; WP_002225337.1; NC_003112.2.
DR PDB; 3FLU; X-ray; 2.00 A; A/B/C/D=1-291.
DR PDBsum; 3FLU; -.
DR AlphaFoldDB; Q9JZR4; -.
DR SMR; Q9JZR4; -.
DR STRING; 122586.NMB0929; -.
DR PaxDb; Q9JZR4; -.
DR EnsemblBacteria; AAF41336; AAF41336; NMB0929.
DR KEGG; nme:NMB0929; -.
DR PATRIC; fig|122586.8.peg.1178; -.
DR HOGENOM; CLU_049343_7_1_4; -.
DR OMA; GMDACVP; -.
DR BRENDA; 4.3.3.7; 3593.
DR UniPathway; UPA00034; UER00017.
DR EvolutionaryTrace; Q9JZR4; -.
DR Proteomes; UP000000425; 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; Allosteric enzyme; Amino-acid biosynthesis; Cytoplasm;
KW Diaminopimelate biosynthesis; Lyase; Lysine biosynthesis;
KW Reference proteome; Schiff base.
FT CHAIN 1..291
FT /note="4-hydroxy-tetrahydrodipicolinate synthase"
FT /id="PRO_0000103131"
FT ACT_SITE 133
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 45
FT /ligand="pyruvate"
FT /ligand_id="ChEBI:CHEBI:15361"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00418"
FT BINDING 203
FT /ligand="pyruvate"
FT /ligand_id="ChEBI:CHEBI:15361"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00418"
FT SITE 44
FT /note="Part of a proton relay during catalysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00418"
FT SITE 107
FT /note="Part of a proton relay during catalysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00418"
FT STRAND 4..8
FT /evidence="ECO:0007829|PDB:3FLU"
FT HELIX 21..33
FT /evidence="ECO:0007829|PDB:3FLU"
FT STRAND 38..43
FT /evidence="ECO:0007829|PDB:3FLU"
FT TURN 44..47
FT /evidence="ECO:0007829|PDB:3FLU"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:3FLU"
FT HELIX 53..67
FT /evidence="ECO:0007829|PDB:3FLU"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:3FLU"
FT HELIX 82..94
FT /evidence="ECO:0007829|PDB:3FLU"
FT STRAND 98..103
FT /evidence="ECO:0007829|PDB:3FLU"
FT HELIX 112..125
FT /evidence="ECO:0007829|PDB:3FLU"
FT STRAND 130..134
FT /evidence="ECO:0007829|PDB:3FLU"
FT HELIX 136..139
FT /evidence="ECO:0007829|PDB:3FLU"
FT HELIX 145..151
FT /evidence="ECO:0007829|PDB:3FLU"
FT STRAND 157..162
FT /evidence="ECO:0007829|PDB:3FLU"
FT HELIX 167..176
FT /evidence="ECO:0007829|PDB:3FLU"
FT STRAND 182..185
FT /evidence="ECO:0007829|PDB:3FLU"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:3FLU"
FT HELIX 191..196
FT /evidence="ECO:0007829|PDB:3FLU"
FT STRAND 201..205
FT /evidence="ECO:0007829|PDB:3FLU"
FT HELIX 206..208
FT /evidence="ECO:0007829|PDB:3FLU"
FT HELIX 211..223
FT /evidence="ECO:0007829|PDB:3FLU"
FT HELIX 226..240
FT /evidence="ECO:0007829|PDB:3FLU"
FT TURN 241..244
FT /evidence="ECO:0007829|PDB:3FLU"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:3FLU"
FT HELIX 250..258
FT /evidence="ECO:0007829|PDB:3FLU"
FT HELIX 275..287
FT /evidence="ECO:0007829|PDB:3FLU"
SQ SEQUENCE 291 AA; 30880 MW; AD5AF175BF32D842 CRC64;
MLQGSLVALI TPMNQDGSIH YEQLRDLIDW HIENGTDGIV AVGTTGESAT LSVEEHTAVI
EAVVKHVAKR VPVIAGTGAN NTVEAIALSQ AAEKAGADYT LSVVPYYNKP SQEGIYQHFK
TIAEATSIPM IIYNVPGRTV VSMTNDTILR LAEIPNIVGV KEASGNIGSN IELINRAPEG
FVVLSGDDHT ALPFMLCGGH GVITVAANAA PKLFADMCRA ALQGDIALAR ELNDRLIPIY
DTMFCEPSPA APKWAVSALG RCEPHVRLPL VPLTENGQAK VRAALKASGQ L
