DAPA_STAAR
ID DAPA_STAAR Reviewed; 295 AA.
AC Q6GH13;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 105.
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=SAR1407;
OS Staphylococcus aureus (strain MRSA252).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=282458;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MRSA252;
RX PubMed=15213324; DOI=10.1073/pnas.0402521101;
RA Holden M.T.G., Feil E.J., Lindsay J.A., Peacock S.J., Day N.P.J.,
RA Enright M.C., Foster T.J., Moore C.E., Hurst L., Atkin R., Barron A.,
RA Bason N., Bentley S.D., Chillingworth C., Chillingworth T., Churcher C.,
RA Clark L., Corton C., Cronin A., Doggett J., Dowd L., Feltwell T., Hance Z.,
RA Harris B., Hauser H., Holroyd S., Jagels K., James K.D., Lennard N.,
RA Line A., Mayes R., Moule S., Mungall K., Ormond D., Quail M.A.,
RA Rabbinowitsch E., Rutherford K.M., Sanders M., Sharp S., Simmonds M.,
RA Stevens K., Whitehead S., Barrell B.G., Spratt B.G., Parkhill J.;
RT "Complete genomes of two clinical Staphylococcus aureus strains: evidence
RT for the rapid evolution of virulence and drug resistance.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:9786-9791(2004).
RN [2]
RP CRYSTALLIZATION.
RC STRAIN=MRSA252;
RX PubMed=18607102; DOI=10.1107/s1744309108016746;
RA Burgess B.R., Dobson R.C., Dogovski C., Jameson G.B., Parker M.W.,
RA Perugini M.A.;
RT "Purification, crystallization and preliminary X-ray diffraction studies to
RT near-atomic resolution of dihydrodipicolinate synthase from methicillin-
RT resistant Staphylococcus aureus.";
RL Acta Crystallogr. F 64:659-661(2008).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 2-293, FUNCTION, KINETIC
RP PARAMETERS, ACTIVITY REGULATION, MASS SPECTROMETRY, AND SUBUNIT.
RC STRAIN=MRSA252;
RX PubMed=18684709; DOI=10.1074/jbc.m804231200;
RA Burgess B.R., Dobson R.C., Bailey M.F., Atkinson S.C., Griffin M.D.,
RA Jameson G.B., Parker M.W., Gerrard J.A., Perugini M.A.;
RT "Structure and evolution of a novel dimeric enzyme from a clinically
RT important bacterial pathogen.";
RL J. Biol. Chem. 283:27598-27603(2008).
CC -!- FUNCTION: Catalyzes the condensation of (S)-aspartate-beta-semialdehyde
CC [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).
CC {ECO:0000305|PubMed:18684709}.
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 insensitive to lysine-feedback inhibition.
CC Shows ASA substrate inhibition. {ECO:0000269|PubMed:18684709}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.11 mM for pyruvate {ECO:0000269|PubMed:18684709};
CC KM=0.22 mM for L-aspartate-4-semialdehyde
CC {ECO:0000269|PubMed:18684709};
CC Note=kcat is 70 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: Homodimer. In fact, exists in a monomer-dimer equilibrium in
CC solution, shifted in favor of the dimer in presence of the substrate
CC pyruvate; the monomer has significantly reduced activity compared with
CC the dimer. {ECO:0000255|HAMAP-Rule:MF_00418,
CC ECO:0000269|PubMed:18684709}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00418}.
CC -!- MASS SPECTROMETRY: Mass=32349.71; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:18684709};
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; BX571856; CAG40404.1; -; Genomic_DNA.
DR RefSeq; WP_000149267.1; NC_002952.2.
DR PDB; 3DAQ; X-ray; 1.45 A; A/B/C/D=2-293.
DR PDBsum; 3DAQ; -.
DR AlphaFoldDB; Q6GH13; -.
DR SMR; Q6GH13; -.
DR KEGG; sar:SAR1407; -.
DR HOGENOM; CLU_049343_7_0_9; -.
DR OMA; GMDACVP; -.
DR OrthoDB; 1438588at2; -.
DR BRENDA; 4.3.3.7; 3352.
DR UniPathway; UPA00034; UER00017.
DR EvolutionaryTrace; Q6GH13; -.
DR Proteomes; UP000000596; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0008840; F:4-hydroxy-tetrahydrodipicolinate synthase activity; IEA:UniProtKB-UniRule.
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 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; PS00666; DHDPS_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Cytoplasm;
KW Diaminopimelate biosynthesis; Lyase; Lysine biosynthesis; Schiff base.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000305"
FT CHAIN 2..295
FT /note="4-hydroxy-tetrahydrodipicolinate synthase"
FT /id="PRO_0000103157"
FT ACT_SITE 135
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00418"
FT ACT_SITE 163
FT /note="Schiff-base intermediate with substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00418"
FT BINDING 47
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 46
FT /note="Part of a proton relay during catalysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00418"
FT SITE 109
FT /note="Part of a proton relay during catalysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00418"
FT STRAND 7..11
FT /evidence="ECO:0007829|PDB:3DAQ"
FT HELIX 23..35
FT /evidence="ECO:0007829|PDB:3DAQ"
FT STRAND 40..45
FT /evidence="ECO:0007829|PDB:3DAQ"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:3DAQ"
FT HELIX 50..52
FT /evidence="ECO:0007829|PDB:3DAQ"
FT HELIX 55..69
FT /evidence="ECO:0007829|PDB:3DAQ"
FT STRAND 75..78
FT /evidence="ECO:0007829|PDB:3DAQ"
FT HELIX 84..97
FT /evidence="ECO:0007829|PDB:3DAQ"
FT STRAND 100..105
FT /evidence="ECO:0007829|PDB:3DAQ"
FT HELIX 114..128
FT /evidence="ECO:0007829|PDB:3DAQ"
FT STRAND 132..136
FT /evidence="ECO:0007829|PDB:3DAQ"
FT HELIX 138..141
FT /evidence="ECO:0007829|PDB:3DAQ"
FT HELIX 147..154
FT /evidence="ECO:0007829|PDB:3DAQ"
FT STRAND 159..164
FT /evidence="ECO:0007829|PDB:3DAQ"
FT HELIX 169..176
FT /evidence="ECO:0007829|PDB:3DAQ"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:3DAQ"
FT STRAND 184..189
FT /evidence="ECO:0007829|PDB:3DAQ"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:3DAQ"
FT HELIX 194..199
FT /evidence="ECO:0007829|PDB:3DAQ"
FT STRAND 204..208
FT /evidence="ECO:0007829|PDB:3DAQ"
FT HELIX 209..211
FT /evidence="ECO:0007829|PDB:3DAQ"
FT HELIX 214..225
FT /evidence="ECO:0007829|PDB:3DAQ"
FT HELIX 231..244
FT /evidence="ECO:0007829|PDB:3DAQ"
FT TURN 249..252
FT /evidence="ECO:0007829|PDB:3DAQ"
FT HELIX 253..259
FT /evidence="ECO:0007829|PDB:3DAQ"
FT STRAND 262..265
FT /evidence="ECO:0007829|PDB:3DAQ"
FT HELIX 276..292
FT /evidence="ECO:0007829|PDB:3DAQ"
SQ SEQUENCE 295 AA; 32481 MW; 194E584D964467BE CRC64;
MTHLFEGVGV ALTTPFTNNK VNLEALKAHV NFLLENNAQA IIVNGTTAES PTLTTDEKEL
ILKTVIDLVD KRVPVIAGTG TNDTEKSIQA SIQAKALGAD AIMLITPYYN KTNQRGLVKH
FEAIADAVKL PVVLYNVPSR TNMTIEPETV EILSQHPYIV ALKDATNDFE YLEEVKKRID
TNSFALYSGN DDNVVEYYQR GGQGVISVIA NVIPKEFQAL YDAQQSGLDI QDQFKPIGTL
LSALSVDINP IPIKALTSYL GFGNYELRLP LVSLEDTDTK VLREAYDTFK AGENE
