DHAS_ECOLI
ID DHAS_ECOLI Reviewed; 367 AA.
AC P0A9Q9; P00353; Q2M797;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Aspartate-semialdehyde dehydrogenase {ECO:0000255|HAMAP-Rule:MF_02121};
DE Short=ASA dehydrogenase {ECO:0000255|HAMAP-Rule:MF_02121};
DE Short=ASADH {ECO:0000255|HAMAP-Rule:MF_02121};
DE EC=1.2.1.11 {ECO:0000269|PubMed:11368768, ECO:0000269|PubMed:6102909};
DE AltName: Full=Aspartate-beta-semialdehyde dehydrogenase {ECO:0000255|HAMAP-Rule:MF_02121};
GN Name=asd {ECO:0000255|HAMAP-Rule:MF_02121}; Synonyms=hom;
GN OrderedLocusNames=b3433, JW3396;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6143662; DOI=10.1002/j.1460-2075.1982.tb01178.x;
RA Haziza C., Stragier P., Patte J.-C.;
RT "Nucleotide sequence of the asd gene of Escherichia coli: absence of a
RT typical attenuation signal.";
RL EMBO J. 1:379-384(1982).
RN [2]
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 [3]
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 [4]
RP PROTEIN SEQUENCE OF 1-5, FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RC STRAIN=K12;
RX PubMed=6102909; DOI=10.1111/j.1432-1033.1980.tb04398.x;
RA Biellmann J.F., Eid P., Hirth C., Jornvall H.;
RT "Aspartate-beta-semialdehyde dehydrogenase from Escherichia coli.
RT Purification and general properties.";
RL Eur. J. Biochem. 104:53-58(1980).
RN [5]
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 [6]
RP ACTIVE SITE, AND MUTAGENESIS OF CYS-135.
RX PubMed=1350921; DOI=10.1016/0167-4838(92)90360-p;
RA Karsten W.E., Viola R.E.;
RT "Identification of an essential cysteine in the reaction catalyzed by
RT aspartate-beta-semialdehyde dehydrogenase from Escherichia coli.";
RL Biochim. Biophys. Acta 1121:234-238(1992).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND KINETIC PARAMETERS.
RX PubMed=11368768; DOI=10.1042/0264-6021:3560415;
RA Chassagnole C., Rais B., Quentin E., Fell D.A., Mazat J.P.;
RT "An integrated study of threonine-pathway enzyme kinetics in Escherichia
RT coli.";
RL Biochem. J. 356:415-423(2001).
RN [8]
RP ACTIVITY REGULATION, AND INHIBITION BY CYSTEINE BINDING AT CYS-135.
RX PubMed=14726201; DOI=10.1016/j.bbapap.2003.09.002;
RA Alvarez E., Ramon F., Magan C., Diez E.;
RT "L-cystine inhibits aspartate-beta-semialdehyde dehydrogenase by covalently
RT binding to the essential 135Cys of the enzyme.";
RL Biochim. Biophys. Acta 1696:23-29(2004).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), AND DOMAIN.
RX PubMed=10369777; DOI=10.1006/jmbi.1999.2828;
RA Hadfield A., Kryger G., Ouyang J., Petsko G.A., Ringe D., Viola R.;
RT "Structure of aspartate-beta-semialdehyde dehydrogenase from Escherichia
RT coli, a key enzyme in the aspartate family of amino acid biosynthesis.";
RL J. Mol. Biol. 289:991-1002(1999).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH CYSTEINE AND NADP,
RP ACTIVE SITE, AND CATALYTIC MECHANISM.
RX PubMed=11724560; DOI=10.1021/bi015713o;
RA Hadfield A., Shammas C., Kryger G., Ringe D., Petsko G.A., Ouyang J.,
RA Viola R.E.;
RT "Active site analysis of the potential antimicrobial target aspartate
RT semialdehyde dehydrogenase.";
RL Biochemistry 40:14475-14483(2001).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF MUTANT GLN-2.
RX PubMed=15288787; DOI=10.1016/j.jmb.2004.05.073;
RA Nichols C.E., Dhaliwal B., Lockyer M., Hawkins A.R., Stammers D.K.;
RT "High-resolution structures reveal details of domain closure and 'half-of-
RT sites-reactivity' in Escherichia coli aspartate beta-semialdehyde
RT dehydrogenase.";
RL J. Mol. Biol. 341:797-806(2004).
CC -!- FUNCTION: Catalyzes the NADPH-dependent formation of L-aspartate-
CC semialdehyde (L-ASA) by the reductive dephosphorylation of L-aspartyl-
CC 4-phosphate. {ECO:0000269|PubMed:11368768, ECO:0000269|PubMed:6102909}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-aspartate 4-semialdehyde + NADP(+) + phosphate = 4-phospho-
CC L-aspartate + H(+) + NADPH; Xref=Rhea:RHEA:24284, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57535, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:537519; EC=1.2.1.11;
CC Evidence={ECO:0000269|PubMed:11368768, ECO:0000269|PubMed:6102909};
CC -!- ACTIVITY REGULATION: Is inhibited by L- and D-cystine, and by other
CC cystine derivatives, via the formation of a covalently bound cysteine
CC at the active site Cys-135. {ECO:0000269|PubMed:14726201}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=22 uM for L-4-aspartyl phosphate {ECO:0000269|PubMed:11368768};
CC KM=29 uM for NADPH {ECO:0000269|PubMed:11368768};
CC KM=110 uM for L-aspartate 4-semialdehyde
CC {ECO:0000269|PubMed:11368768};
CC KM=144 uM for NADP(+) {ECO:0000269|PubMed:11368768};
CC KM=10.2 mM for phosphate {ECO:0000269|PubMed:11368768};
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via DAP
CC pathway; (S)-tetrahydrodipicolinate from L-aspartate: step 2/4.
CC {ECO:0000255|HAMAP-Rule:MF_02121}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC pathway; L-homoserine from L-aspartate: step 2/3. {ECO:0000255|HAMAP-
CC Rule:MF_02121}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-threonine biosynthesis; L-threonine
CC from L-aspartate: step 2/5. {ECO:0000255|HAMAP-Rule:MF_02121}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11724560,
CC ECO:0000269|PubMed:6102909}.
CC -!- DOMAIN: Consists of two domains, an N-terminal nucleotide-binding
CC domain and a C-terminal dimerization domain.
CC {ECO:0000269|PubMed:10369777}.
CC -!- SIMILARITY: Belongs to the aspartate-semialdehyde dehydrogenase family.
CC {ECO:0000255|HAMAP-Rule:MF_02121}.
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DR EMBL; V00262; CAA23511.1; -; Genomic_DNA.
DR EMBL; U18997; AAA58231.1; -; Genomic_DNA.
DR EMBL; U00096; AAC76458.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE77859.1; -; Genomic_DNA.
DR PIR; A00364; DEECDA.
DR RefSeq; NP_417891.1; NC_000913.3.
DR RefSeq; WP_000799956.1; NZ_STEB01000004.1.
DR PDB; 1BRM; X-ray; 2.50 A; A/B/C=1-367.
DR PDB; 1GL3; X-ray; 2.60 A; A/B=1-367.
DR PDB; 1T4B; X-ray; 1.60 A; A/B=1-367.
DR PDB; 1T4D; X-ray; 1.95 A; A/B/C=1-367.
DR PDBsum; 1BRM; -.
DR PDBsum; 1GL3; -.
DR PDBsum; 1T4B; -.
DR PDBsum; 1T4D; -.
DR AlphaFoldDB; P0A9Q9; -.
DR PCDDB; P0A9Q9; -.
DR SMR; P0A9Q9; -.
DR BioGRID; 4262504; 7.
DR IntAct; P0A9Q9; 1.
DR STRING; 511145.b3433; -.
DR SWISS-2DPAGE; P0A9Q9; -.
DR jPOST; P0A9Q9; -.
DR PaxDb; P0A9Q9; -.
DR PRIDE; P0A9Q9; -.
DR EnsemblBacteria; AAC76458; AAC76458; b3433.
DR EnsemblBacteria; BAE77859; BAE77859; BAE77859.
DR GeneID; 66672683; -.
DR GeneID; 947939; -.
DR KEGG; ecj:JW3396; -.
DR KEGG; eco:b3433; -.
DR PATRIC; fig|511145.12.peg.3530; -.
DR EchoBASE; EB0086; -.
DR eggNOG; COG0136; Bacteria.
DR HOGENOM; CLU_066397_0_0_6; -.
DR InParanoid; P0A9Q9; -.
DR OMA; MFDVPDE; -.
DR PhylomeDB; P0A9Q9; -.
DR BioCyc; EcoCyc:ASP-SEMIALDEHYDE-DEHYDROGENASE-MON; -.
DR BioCyc; MetaCyc:ASP-SEMIALDEHYDE-DEHYDROGENASE-MON; -.
DR BRENDA; 1.2.1.11; 2026.
DR SABIO-RK; P0A9Q9; -.
DR UniPathway; UPA00034; UER00016.
DR UniPathway; UPA00050; UER00463.
DR UniPathway; UPA00051; UER00464.
DR EvolutionaryTrace; P0A9Q9; -.
DR PRO; PR:P0A9Q9; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0004073; F:aspartate-semialdehyde dehydrogenase activity; IDA:EcoCyc.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0050661; F:NADP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0071266; P:'de novo' L-methionine biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEP:EcoliWiki.
DR GO; GO:0019877; P:diaminopimelate biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0009090; P:homoserine biosynthetic process; IDA:EcoCyc.
DR GO; GO:0009097; P:isoleucine biosynthetic process; IEA:InterPro.
DR GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IDA:EcoCyc.
DR GO; GO:0009088; P:threonine biosynthetic process; IEA:UniProtKB-UniRule.
DR DisProt; DP02663; -.
DR HAMAP; MF_02121; ASADH; 1.
DR InterPro; IPR000319; Asp-semialdehyde_DH_CS.
DR InterPro; IPR011534; Asp_ADH_gamma-type.
DR InterPro; IPR012080; Asp_semialdehyde_DH.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR000534; Semialdehyde_DH_NAD-bd.
DR InterPro; IPR012280; Semialdhyde_DH_dimer_dom.
DR PANTHER; PTHR46278:SF4; PTHR46278:SF4; 1.
DR Pfam; PF01118; Semialdhyde_dh; 1.
DR Pfam; PF02774; Semialdhyde_dhC; 1.
DR SMART; SM00859; Semialdhyde_dh; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01745; asd_gamma; 1.
DR PROSITE; PS01103; ASD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Diaminopimelate biosynthesis;
KW Direct protein sequencing; Lysine biosynthesis; Methionine biosynthesis;
KW NADP; Oxidoreductase; Reference proteome; Threonine biosynthesis.
FT CHAIN 1..367
FT /note="Aspartate-semialdehyde dehydrogenase"
FT /id="PRO_0000141369"
FT ACT_SITE 135
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000269|PubMed:11724560"
FT ACT_SITE 274
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:11724560"
FT BINDING 10..13
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11724560"
FT BINDING 37..38
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11724560"
FT BINDING 73
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11724560"
FT BINDING 102
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02121"
FT BINDING 162
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:11724560"
FT BINDING 165..169
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11724560"
FT BINDING 173
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11724560"
FT BINDING 193
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11724560"
FT BINDING 241
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:11724560"
FT BINDING 244
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02121"
FT BINDING 267
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:11724560"
FT BINDING 350
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11724560"
FT MOD_RES 135
FT /note="S-cysteinyl cysteine; in inhibited form"
FT MUTAGEN 135
FT /note="C->A: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:1350921"
FT MUTAGEN 135
FT /note="C->S: 99.7% loss of activity."
FT /evidence="ECO:0000269|PubMed:1350921"
FT CONFLICT 9
FT /note="W -> G (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 3..8
FT /evidence="ECO:0007829|PDB:1T4B"
FT HELIX 12..23
FT /evidence="ECO:0007829|PDB:1T4B"
FT HELIX 26..29
FT /evidence="ECO:0007829|PDB:1T4B"
FT STRAND 30..39
FT /evidence="ECO:0007829|PDB:1T4B"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:1T4D"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:1T4B"
FT HELIX 60..64
FT /evidence="ECO:0007829|PDB:1T4B"
FT STRAND 67..71
FT /evidence="ECO:0007829|PDB:1T4B"
FT HELIX 75..87
FT /evidence="ECO:0007829|PDB:1T4B"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:1T4B"
FT TURN 100..103
FT /evidence="ECO:0007829|PDB:1T4B"
FT STRAND 107..110
FT /evidence="ECO:0007829|PDB:1T4B"
FT HELIX 112..124
FT /evidence="ECO:0007829|PDB:1T4B"
FT STRAND 129..132
FT /evidence="ECO:0007829|PDB:1T4B"
FT HELIX 135..149
FT /evidence="ECO:0007829|PDB:1T4B"
FT STRAND 153..162
FT /evidence="ECO:0007829|PDB:1T4B"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:1T4B"
FT HELIX 169..185
FT /evidence="ECO:0007829|PDB:1T4B"
FT HELIX 187..190
FT /evidence="ECO:0007829|PDB:1T4B"
FT HELIX 197..210
FT /evidence="ECO:0007829|PDB:1T4B"
FT TURN 216..218
FT /evidence="ECO:0007829|PDB:1T4B"
FT STRAND 226..228
FT /evidence="ECO:0007829|PDB:1T4B"
FT STRAND 235..239
FT /evidence="ECO:0007829|PDB:1GL3"
FT HELIX 240..253
FT /evidence="ECO:0007829|PDB:1T4B"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:1T4B"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:1T4B"
FT STRAND 271..284
FT /evidence="ECO:0007829|PDB:1T4B"
FT HELIX 288..298
FT /evidence="ECO:0007829|PDB:1T4B"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:1GL3"
FT HELIX 309..315
FT /evidence="ECO:0007829|PDB:1T4B"
FT HELIX 318..321
FT /evidence="ECO:0007829|PDB:1T4B"
FT STRAND 329..334
FT /evidence="ECO:0007829|PDB:1T4B"
FT STRAND 341..349
FT /evidence="ECO:0007829|PDB:1T4B"
FT HELIX 352..356
FT /evidence="ECO:0007829|PDB:1T4B"
FT HELIX 357..366
FT /evidence="ECO:0007829|PDB:1T4B"
SQ SEQUENCE 367 AA; 40018 MW; F53D4C36EA7CC201 CRC64;
MKNVGFIGWR GMVGSVLMQR MVEERDFDAI RPVFFSTSQL GQAAPSFGGT TGTLQDAFDL
EALKALDIIV TCQGGDYTNE IYPKLRESGW QGYWIDAASS LRMKDDAIII LDPVNQDVIT
DGLNNGIRTF VGGNCTVSLM LMSLGGLFAN DLVDWVSVAT YQAASGGGAR HMRELLTQMG
HLYGHVADEL ATPSSAILDI ERKVTTLTRS GELPVDNFGV PLAGSLIPWI DKQLDNGQSR
EEWKGQAETN KILNTSSVIP VDGLCVRVGA LRCHSQAFTI KLKKDVSIPT VEELLAAHNP
WAKVVPNDRE ITMRELTPAA VTGTLTTPVG RLRKLNMGPE FLSAFTVGDQ LLWGAAEPLR
RMLRQLA
