DHAS_HAEIN
ID DHAS_HAEIN Reviewed; 371 AA.
AC P44801;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 151.
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:12071715, ECO:0000269|PubMed:15272161};
DE AltName: Full=Aspartate-beta-semialdehyde dehydrogenase {ECO:0000255|HAMAP-Rule:MF_02121};
GN Name=asd {ECO:0000255|HAMAP-Rule:MF_02121}; OrderedLocusNames=HI_0646;
OS Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pasteurellales;
OC Pasteurellaceae; Haemophilus.
OX NCBI_TaxID=71421;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX PubMed=7542800; DOI=10.1126/science.7542800;
RA Fleischmann R.D., Adams M.D., White O., Clayton R.A., Kirkness E.F.,
RA Kerlavage A.R., Bult C.J., Tomb J.-F., Dougherty B.A., Merrick J.M.,
RA McKenney K., Sutton G.G., FitzHugh W., Fields C.A., Gocayne J.D.,
RA Scott J.D., Shirley R., Liu L.-I., Glodek A., Kelley J.M., Weidman J.F.,
RA Phillips C.A., Spriggs T., Hedblom E., Cotton M.D., Utterback T.R.,
RA Hanna M.C., Nguyen D.T., Saudek D.M., Brandon R.C., Fine L.D.,
RA Fritchman J.L., Fuhrmann J.L., Geoghagen N.S.M., Gnehm C.L., McDonald L.A.,
RA Small K.V., Fraser C.M., Smith H.O., Venter J.C.;
RT "Whole-genome random sequencing and assembly of Haemophilus influenzae
RT Rd.";
RL Science 269:496-512(1995).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND KINETIC PARAMETERS.
RC STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX PubMed=12071715; DOI=10.1006/prep.2002.1626;
RA Moore R.A., Bocik W.E., Viola R.E.;
RT "Expression and purification of aspartate beta-semialdehyde dehydrogenase
RT from infectious microorganisms.";
RL Protein Expr. Purif. 25:189-194(2002).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH
RP L-ASPARTATE-SEMIALDEHYDE AND PHOSPHATE, SUBUNIT, DOMAIN, AND CATALYTIC
RP MECHANISM.
RC STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX PubMed=14559965; DOI=10.1073/pnas.1634958100;
RA Blanco J., Moore R.A., Viola R.E.;
RT "Capture of an intermediate in the catalytic cycle of L-aspartate-beta-
RT semialdehyde dehydrogenase.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12613-12617(2003).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF MUTANTS LEU-103; LYS-103;
RP SER-136; ASP-243; ARG-246; LYS-270 AND ASN-277 IN COMPLEX WITH NADP,
RP CATALYTIC ACTIVITY, KINETIC STUDIES, AND MUTAGENESIS OF ARG-103; GLU-243;
RP LYS-246 AND ARG-270.
RC STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX PubMed=15272161; DOI=10.1107/s0907444904012971;
RA Blanco J., Moore R.A., Faehnle C.R., Coe D.M., Viola R.E.;
RT "The role of substrate-binding groups in the mechanism of aspartate-beta-
RT semialdehyde dehydrogenase.";
RL Acta Crystallogr. D 60:1388-1395(2004).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEXES WITH ARSENATE AND
RP PERIODATE IONS.
RC STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX PubMed=15583380; DOI=10.1107/s0907444904026411;
RA Faehnle C.R., Blanco J., Viola R.E.;
RT "Structural basis for discrimination between oxyanion substrates or
RT inhibitors in aspartate-beta-semialdehyde dehydrogenase.";
RL Acta Crystallogr. D 60:2320-2324(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:12071715}.
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:12071715, ECO:0000269|PubMed:15272161};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.24 mM for L-aspartate 4-semialdehyde
CC {ECO:0000269|PubMed:12071715};
CC KM=0.15 mM for NADP(+) {ECO:0000269|PubMed:12071715};
CC KM=1.6 mM for phosphate {ECO:0000269|PubMed:12071715};
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:14559965,
CC ECO:0000269|PubMed:15272161}.
CC -!- DOMAIN: Consists of two domains, an N-terminal nucleotide-binding
CC domain and a C-terminal dimerization domain.
CC {ECO:0000269|PubMed:14559965}.
CC -!- SIMILARITY: Belongs to the aspartate-semialdehyde dehydrogenase family.
CC {ECO:0000255|HAMAP-Rule:MF_02121}.
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DR EMBL; L42023; AAC22306.1; -; Genomic_DNA.
DR PIR; B64084; B64084.
DR RefSeq; NP_438806.1; NC_000907.1.
DR RefSeq; WP_005694497.1; NC_000907.1.
DR PDB; 1NWC; X-ray; 2.04 A; A/B=1-371.
DR PDB; 1NWH; X-ray; 2.00 A; A/B=1-371.
DR PDB; 1NX6; X-ray; 2.15 A; A=1-371.
DR PDB; 1OZA; X-ray; 2.06 A; A=1-371.
DR PDB; 1PQP; X-ray; 2.06 A; A=1-371.
DR PDB; 1PQU; X-ray; 1.92 A; A/B/C/D=1-371.
DR PDB; 1PR3; X-ray; 2.15 A; A=1-371.
DR PDB; 1PS8; X-ray; 2.40 A; A=1-371.
DR PDB; 1PU2; X-ray; 2.06 A; A=1-371.
DR PDB; 1Q2X; X-ray; 2.05 A; A/B=1-371.
DR PDB; 1TA4; X-ray; 2.28 A; A=1-371.
DR PDB; 1TB4; X-ray; 2.15 A; A=1-371.
DR PDBsum; 1NWC; -.
DR PDBsum; 1NWH; -.
DR PDBsum; 1NX6; -.
DR PDBsum; 1OZA; -.
DR PDBsum; 1PQP; -.
DR PDBsum; 1PQU; -.
DR PDBsum; 1PR3; -.
DR PDBsum; 1PS8; -.
DR PDBsum; 1PU2; -.
DR PDBsum; 1Q2X; -.
DR PDBsum; 1TA4; -.
DR PDBsum; 1TB4; -.
DR AlphaFoldDB; P44801; -.
DR SMR; P44801; -.
DR STRING; 71421.HI_0646; -.
DR DrugBank; DB03502; (4s)-4-{[(2s)-2-Amino-3-Oxopropyl]Sulfanyl}-L-Homoserinate.
DR DrugBank; DB04498; Aspartate Semialdehyde.
DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate.
DR EnsemblBacteria; AAC22306; AAC22306; HI_0646.
DR KEGG; hin:HI_0646; -.
DR PATRIC; fig|71421.8.peg.675; -.
DR eggNOG; COG0136; Bacteria.
DR HOGENOM; CLU_066397_0_0_6; -.
DR OMA; MFDVPDE; -.
DR PhylomeDB; P44801; -.
DR BioCyc; HINF71421:G1GJ1-681-MON; -.
DR BRENDA; 1.2.1.11; 2529.
DR SABIO-RK; P44801; -.
DR UniPathway; UPA00034; UER00016.
DR UniPathway; UPA00050; UER00463.
DR UniPathway; UPA00051; UER00464.
DR EvolutionaryTrace; P44801; -.
DR Proteomes; UP000000579; Chromosome.
DR GO; GO:0004073; F:aspartate-semialdehyde dehydrogenase activity; IEA:UniProtKB-UniRule.
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:0019877; P:diaminopimelate biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0009097; P:isoleucine biosynthetic process; IEA:InterPro.
DR GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IEA:UniProtKB-UniRule.
DR GO; GO:0009088; P:threonine biosynthetic process; IEA:UniProtKB-UniRule.
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 Lysine biosynthesis; Methionine biosynthesis; NADP; Oxidoreductase;
KW Reference proteome; Threonine biosynthesis.
FT CHAIN 1..371
FT /note="Aspartate-semialdehyde dehydrogenase"
FT /id="PRO_0000141375"
FT ACT_SITE 136
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000269|PubMed:14559965,
FT ECO:0000269|PubMed:15272161"
FT ACT_SITE 277
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:14559965"
FT BINDING 10..13
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15272161"
FT BINDING 37..38
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15272161"
FT BINDING 74
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15272161"
FT BINDING 103
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000269|PubMed:14559965"
FT BINDING 163
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:15272161"
FT BINDING 166
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15272161"
FT BINDING 243
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:15272161"
FT BINDING 246
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000269|PubMed:14559965"
FT BINDING 270
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:15272161"
FT BINDING 353
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15272161"
FT MUTAGEN 103
FT /note="R->K: 2-fold increase in affinity for ASA, 23-fold
FT decrease in affinity for phosphate, and 275-fold decrease
FT in activity."
FT /evidence="ECO:0000269|PubMed:15272161"
FT MUTAGEN 103
FT /note="R->L: 7-fold increase in affinity for ASA, 150-fold
FT decrease in affinity for phosphate, and 1400-fold decrease
FT in activity."
FT /evidence="ECO:0000269|PubMed:15272161"
FT MUTAGEN 243
FT /note="E->D: No change in affinity for ASA and 82-fold
FT decrease in activity."
FT /evidence="ECO:0000269|PubMed:15272161"
FT MUTAGEN 246
FT /note="K->R: 2-fold increase in affinity for ASA, nearly no
FT change in affinity for phosphate, and 30-fold decrease in
FT activity."
FT /evidence="ECO:0000269|PubMed:15272161"
FT MUTAGEN 270
FT /note="R->K: 2-fold decrease in affinity for ASA and 825-
FT fold decrease in activity."
FT /evidence="ECO:0000269|PubMed:15272161"
FT STRAND 2..8
FT /evidence="ECO:0007829|PDB:1PQU"
FT HELIX 12..24
FT /evidence="ECO:0007829|PDB:1PQU"
FT TURN 25..29
FT /evidence="ECO:0007829|PDB:1PQU"
FT STRAND 30..38
FT /evidence="ECO:0007829|PDB:1PQU"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:1PQU"
FT HELIX 61..64
FT /evidence="ECO:0007829|PDB:1PQU"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:1PQU"
FT HELIX 76..88
FT /evidence="ECO:0007829|PDB:1PQU"
FT STRAND 93..100
FT /evidence="ECO:0007829|PDB:1PQU"
FT TURN 101..104
FT /evidence="ECO:0007829|PDB:1PQU"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:1PQU"
FT HELIX 113..126
FT /evidence="ECO:0007829|PDB:1PQU"
FT STRAND 130..133
FT /evidence="ECO:0007829|PDB:1PQU"
FT HELIX 136..150
FT /evidence="ECO:0007829|PDB:1PQU"
FT STRAND 154..163
FT /evidence="ECO:0007829|PDB:1PQU"
FT HELIX 165..167
FT /evidence="ECO:0007829|PDB:1PQU"
FT HELIX 170..185
FT /evidence="ECO:0007829|PDB:1PQU"
FT HELIX 188..191
FT /evidence="ECO:0007829|PDB:1PQU"
FT HELIX 198..209
FT /evidence="ECO:0007829|PDB:1PQU"
FT TURN 217..219
FT /evidence="ECO:0007829|PDB:1PQU"
FT STRAND 225..228
FT /evidence="ECO:0007829|PDB:1PQU"
FT TURN 236..238
FT /evidence="ECO:0007829|PDB:1PQU"
FT HELIX 242..255
FT /evidence="ECO:0007829|PDB:1PQU"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:1Q2X"
FT STRAND 264..267
FT /evidence="ECO:0007829|PDB:1PQU"
FT STRAND 270..287
FT /evidence="ECO:0007829|PDB:1PQU"
FT HELIX 291..300
FT /evidence="ECO:0007829|PDB:1PQU"
FT STRAND 303..307
FT /evidence="ECO:0007829|PDB:1PQU"
FT HELIX 312..318
FT /evidence="ECO:0007829|PDB:1PQU"
FT HELIX 321..324
FT /evidence="ECO:0007829|PDB:1PQU"
FT STRAND 330..338
FT /evidence="ECO:0007829|PDB:1PQU"
FT STRAND 341..352
FT /evidence="ECO:0007829|PDB:1PQU"
FT TURN 353..358
FT /evidence="ECO:0007829|PDB:1PQU"
FT HELIX 359..370
FT /evidence="ECO:0007829|PDB:1PQU"
SQ SEQUENCE 371 AA; 40539 MW; E44CE5B90F2AF041 CRC64;
MKNVGFIGWR GMVGSVLMDR MSQENDFENL NPVFFTTSQA GQKAPVFGGK DAGDLKSAFD
IEELKKLDII VTCQGGDYTN EVYPKLKATG WDGYWVDAAS ALRMKDDAII VLDPVNQHVI
SEGLKKGIKT FVGGNCTVSL MLMAIGGLFE KDLVEWISVA TYQAASGAGA KNMRELLSQM
GLLEQAVSSE LKDPASSILD IERKVTAKMR ADNFPTDNFG AALGGSLIPW IDKLLPETGQ
TKEEWKGYAE TNKILGLSDN PIPVDGLCVR IGALRCHSQA FTIKLKKDLP LEEIEQIIAS
HNEWVKVIPN DKEITLRELT PAKVTGTLSV PVGRLRKLAM GPEYLAAFTV GDQLLWGAAE
PVRRILKQLV A
