DHAS1_VIBCH
ID DHAS1_VIBCH Reviewed; 370 AA.
AC Q9KQG2;
DT 27-JUL-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Aspartate-semialdehyde dehydrogenase 1;
DE Short=ASA dehydrogenase 1;
DE Short=ASADH 1;
DE EC=1.2.1.11 {ECO:0000269|PubMed:12071715};
DE AltName: Full=Aspartate-beta-semialdehyde dehydrogenase 1;
GN Name=asd1; OrderedLocusNames=VC_2036;
OS Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Vibrionales; Vibrionaceae;
OC Vibrio.
OX NCBI_TaxID=243277;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 39315 / El Tor Inaba N16961;
RX PubMed=10952301; DOI=10.1038/35020000;
RA Heidelberg J.F., Eisen J.A., Nelson W.C., Clayton R.A., Gwinn M.L.,
RA Dodson R.J., Haft D.H., Hickey E.K., Peterson J.D., Umayam L.A., Gill S.R.,
RA Nelson K.E., Read T.D., Tettelin H., Richardson D.L., Ermolaeva M.D.,
RA Vamathevan J.J., Bass S., Qin H., Dragoi I., Sellers P., McDonald L.A.,
RA Utterback T.R., Fleischmann R.D., Nierman W.C., White O., Salzberg S.L.,
RA Smith H.O., Colwell R.R., Mekalanos J.J., Venter J.C., Fraser C.M.;
RT "DNA sequence of both chromosomes of the cholera pathogen Vibrio
RT cholerae.";
RL Nature 406:477-483(2000).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND KINETIC PARAMETERS.
RC STRAIN=ATCC 39315 / El Tor Inaba N16961;
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 (1.84 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH
RP NADP AND CYSTEINE, ACTIVITY REGULATION, ACTIVE SITE, AND SUBUNIT.
RC STRAIN=ATCC 39315 / El Tor Inaba N16961;
RX PubMed=12493825; DOI=10.1110/ps.0230803;
RA Blanco J., Moore R.A., Kabaleeswaran V., Viola R.E.;
RT "A structural basis for the mechanism of aspartate-beta-semialdehyde
RT dehydrogenase from Vibrio cholerae.";
RL Protein Sci. 12:27-33(2003).
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};
CC -!- ACTIVITY REGULATION: Inhibited by S-methyl-L-cysteine sulfoxide in
CC vitro, via the formation of a covalently bound cysteine at the active
CC site Cys-134. {ECO:0000269|PubMed:12493825}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.19 mM for L-aspartate 4-semialdehyde
CC {ECO:0000269|PubMed:12071715};
CC KM=0.32 mM for NADP(+) {ECO:0000269|PubMed:12071715};
CC KM=1.1 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:0000255|HAMAP-Rule:MF_02121,
CC ECO:0000305|PubMed:12493825}.
CC -!- SIMILARITY: Belongs to the aspartate-semialdehyde dehydrogenase family.
CC {ECO:0000255|HAMAP-Rule:MF_02121}.
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DR EMBL; AE003852; AAF95184.1; -; Genomic_DNA.
DR PIR; F82125; F82125.
DR RefSeq; NP_231670.1; NC_002505.1.
DR RefSeq; WP_001263690.1; NZ_LT906614.1.
DR PDB; 1MB4; X-ray; 1.84 A; A/B=1-370.
DR PDB; 1MC4; X-ray; 2.77 A; A=1-370.
DR PDB; 3PZR; X-ray; 1.75 A; A/B=1-370.
DR PDB; 3Q0E; X-ray; 1.80 A; A/B=1-370.
DR PDB; 4R5M; X-ray; 1.89 A; A/B=1-370.
DR PDBsum; 1MB4; -.
DR PDBsum; 1MC4; -.
DR PDBsum; 3PZR; -.
DR PDBsum; 3Q0E; -.
DR PDBsum; 4R5M; -.
DR AlphaFoldDB; Q9KQG2; -.
DR SMR; Q9KQG2; -.
DR STRING; 243277.VC_2036; -.
DR PRIDE; Q9KQG2; -.
DR DNASU; 2613415; -.
DR EnsemblBacteria; AAF95184; AAF95184; VC_2036.
DR GeneID; 57740661; -.
DR GeneID; 66940464; -.
DR KEGG; vch:VC_2036; -.
DR PATRIC; fig|243277.26.peg.1944; -.
DR eggNOG; COG0136; Bacteria.
DR HOGENOM; CLU_066397_0_0_6; -.
DR OMA; MFDVPDE; -.
DR BioCyc; MetaCyc:MON-15807; -.
DR BioCyc; VCHO:VC2036-MON; -.
DR BRENDA; 1.2.1.11; 6626.
DR SABIO-RK; Q9KQG2; -.
DR UniPathway; UPA00034; UER00016.
DR UniPathway; UPA00050; UER00463.
DR UniPathway; UPA00051; UER00464.
DR EvolutionaryTrace; Q9KQG2; -.
DR Proteomes; UP000000584; Chromosome 1.
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..370
FT /note="Aspartate-semialdehyde dehydrogenase 1"
FT /id="PRO_0000411126"
FT ACT_SITE 134
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000269|PubMed:12493825"
FT ACT_SITE 274
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:12493825"
FT BINDING 9..12
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12493825"
FT BINDING 36..37
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12493825"
FT BINDING 72
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12493825"
FT BINDING 101
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02121"
FT BINDING 161
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:12493825"
FT BINDING 164..165
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12493825"
FT BINDING 192
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12493825"
FT BINDING 240
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:12493825"
FT BINDING 243
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:12493825"
FT BINDING 350
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12493825"
FT MOD_RES 134
FT /note="S-cysteinyl cysteine; in inhibited form"
FT STRAND 2..7
FT /evidence="ECO:0007829|PDB:3PZR"
FT HELIX 11..22
FT /evidence="ECO:0007829|PDB:3PZR"
FT HELIX 25..28
FT /evidence="ECO:0007829|PDB:3PZR"
FT STRAND 29..38
FT /evidence="ECO:0007829|PDB:3PZR"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:3Q0E"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:3PZR"
FT HELIX 59..62
FT /evidence="ECO:0007829|PDB:3PZR"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:3PZR"
FT HELIX 74..86
FT /evidence="ECO:0007829|PDB:3PZR"
FT STRAND 92..95
FT /evidence="ECO:0007829|PDB:3PZR"
FT TURN 99..102
FT /evidence="ECO:0007829|PDB:3PZR"
FT STRAND 106..109
FT /evidence="ECO:0007829|PDB:3PZR"
FT HELIX 111..123
FT /evidence="ECO:0007829|PDB:3PZR"
FT STRAND 128..131
FT /evidence="ECO:0007829|PDB:3PZR"
FT HELIX 134..148
FT /evidence="ECO:0007829|PDB:3PZR"
FT STRAND 152..161
FT /evidence="ECO:0007829|PDB:3PZR"
FT HELIX 163..165
FT /evidence="ECO:0007829|PDB:3PZR"
FT HELIX 168..190
FT /evidence="ECO:0007829|PDB:3PZR"
FT HELIX 196..208
FT /evidence="ECO:0007829|PDB:3PZR"
FT TURN 215..217
FT /evidence="ECO:0007829|PDB:3PZR"
FT STRAND 224..227
FT /evidence="ECO:0007829|PDB:3PZR"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:1MB4"
FT HELIX 239..251
FT /evidence="ECO:0007829|PDB:3PZR"
FT STRAND 255..257
FT /evidence="ECO:0007829|PDB:1MC4"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:3PZR"
FT STRAND 271..284
FT /evidence="ECO:0007829|PDB:3PZR"
FT HELIX 288..296
FT /evidence="ECO:0007829|PDB:3PZR"
FT STRAND 300..304
FT /evidence="ECO:0007829|PDB:3PZR"
FT HELIX 309..315
FT /evidence="ECO:0007829|PDB:3PZR"
FT HELIX 318..321
FT /evidence="ECO:0007829|PDB:3PZR"
FT STRAND 327..335
FT /evidence="ECO:0007829|PDB:3PZR"
FT STRAND 338..349
FT /evidence="ECO:0007829|PDB:3PZR"
FT TURN 350..355
FT /evidence="ECO:0007829|PDB:3PZR"
FT HELIX 356..369
FT /evidence="ECO:0007829|PDB:3PZR"
SQ SEQUENCE 370 AA; 40498 MW; 52F936ACCB4FBA84 CRC64;
MRVGLVGWRG MVGSVLMQRM VEERDFDLIE PVFFSTSQIG VPAPNFGKDA GMLHDAFDIE
SLKQLDAVIT CQGGSYTEKV YPALRQAGWK GYWIDAASTL RMDKEAIITL DPVNLKQILH
GIHHGTKTFV GGNCTVSLML MALGGLYERG LVEWMSAMTY QAASGAGAQN MRELISQMGV
INDAVSSELA NPASSILDID KKVAETMRSG SFPTDNFGVP LAGSLIPWID VKRDNGQSKE
EWKAGVEANK ILGLQDSPVP IDGTCVRIGA MRCHSQALTI KLKQNIPLDE IEEMIATHND
WVKVIPNERD ITARELTPAK VTGTLSVPVG RLRKMAMGDD FLNAFTVGDQ LLWGAAEPLR
RTLRIILAEK
