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 02-SEP-2026, entry version 116. 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=SAR1407; OS Staphylococcus aureus (strain MRSA252). OC Bacteria; Bacillati; Bacillota; Bacilli; Caryophanales; 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- CC hydroxy-2,3,4,5-tetrahydrodipicolinate + H2O + H(+); 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 -!- 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}. 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; 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 AlphaFoldDB; Q6GH13; -. DR SMR; Q6GH13; -. DR KEGG; sar:SAR1407; -. DR HOGENOM; CLU_049343_7_0_9; -. DR BRENDA; 4.3.3.7; 3352. DR UniPathway; UPA00034; UER00017. DR EvolutionaryTrace; Q6GH13; -. DR GO; GO:0005829; C:cytosol; IEA:TreeGrafter. DR GO; GO:0008840; F:4-hydroxy-tetrahydrodipicolinate synthase activity; IEA:UniProtKB-UniRule. 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 NCBIfam; TIGR00674; dapA; 1. DR PANTHER; PTHR12128:SF66; 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; PS00666; DHDPS_2; 1. DR PDBsum; 3DAQ; -. 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 273..275 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 //