ID   ADHE_ECO57              Reviewed;         891 AA.
AC   P0A9Q8; P17547;
DT   19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   27-MAR-2024, entry version 113.
DE   RecName: Full=Bifunctional aldehyde-alcohol dehydrogenase AdhE {ECO:0000305};
DE   AltName: Full=Alcohol dehydrogenase E {ECO:0000305};
DE   Includes:
DE     RecName: Full=Acetaldehyde dehydrogenase [acetylating] {ECO:0000305};
DE              Short=ACDH {ECO:0000250|UniProtKB:P0A9Q7};
DE              EC=1.2.1.10 {ECO:0000250|UniProtKB:P0A9Q7};
DE   Includes:
DE     RecName: Full=Alcohol dehydrogenase {ECO:0000303|PubMed:24846743};
DE              Short=ADH {ECO:0000250|UniProtKB:P0A9Q7};
DE              EC=1.1.1.1 {ECO:0000250|UniProtKB:P0A9Q7};
GN   Name=adhE {ECO:0000303|PubMed:24846743};
GN   OrderedLocusNames=Z2016, ECs1741;
OS   Escherichia coli O157:H7.
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Escherichia.
OX   NCBI_TaxID=83334;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=O157:H7 / EDL933 / ATCC 700927 / EHEC;
RX   PubMed=11206551; DOI=10.1038/35054089;
RA   Perna N.T., Plunkett G. III, Burland V., Mau B., Glasner J.D., Rose D.J.,
RA   Mayhew G.F., Evans P.S., Gregor J., Kirkpatrick H.A., Posfai G.,
RA   Hackett J., Klink S., Boutin A., Shao Y., Miller L., Grotbeck E.J.,
RA   Davis N.W., Lim A., Dimalanta E.T., Potamousis K., Apodaca J.,
RA   Anantharaman T.S., Lin J., Yen G., Schwartz D.C., Welch R.A.,
RA   Blattner F.R.;
RT   "Genome sequence of enterohaemorrhagic Escherichia coli O157:H7.";
RL   Nature 409:529-533(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=O157:H7 / Sakai / RIMD 0509952 / EHEC;
RX   PubMed=11258796; DOI=10.1093/dnares/8.1.11;
RA   Hayashi T., Makino K., Ohnishi M., Kurokawa K., Ishii K., Yokoyama K.,
RA   Han C.-G., Ohtsubo E., Nakayama K., Murata T., Tanaka M., Tobe T., Iida T.,
RA   Takami H., Honda T., Sasakawa C., Ogasawara N., Yasunaga T., Kuhara S.,
RA   Shiba T., Hattori M., Shinagawa H.;
RT   "Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and
RT   genomic comparison with a laboratory strain K-12.";
RL   DNA Res. 8:11-22(2001).
RN   [3]
RP   FUNCTION IN VIRULENCE, AND DISRUPTION PHENOTYPE.
RC   STRAIN=O157:H7 / EHEC;
RX   PubMed=24846743; DOI=10.1111/mmi.12651;
RA   Beckham K.S., Connolly J.P., Ritchie J.M., Wang D., Gawthorne J.A.,
RA   Tahoun A., Gally D.L., Burgess K., Burchmore R.J., Smith B.O.,
RA   Beatson S.A., Byron O., Wolfe A.J., Douce G.R., Roe A.J.;
RT   "The metabolic enzyme AdhE controls the virulence of Escherichia coli
RT   O157:H7.";
RL   Mol. Microbiol. 93:199-211(2014).
RN   [4] {ECO:0007744|PDB:6SCG, ECO:0007744|PDB:6SCI}
RP   X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 451-891 IN COMPLEXES WITH NAD AND
RP   IRON, AND COFACTOR.
RC   STRAIN=O157:H7 / EHEC;
RX   PubMed=32880589; DOI=10.1107/s2053230x20010237;
RA   Azmi L., Bragginton E.C., Cadby I.T., Byron O., Roe A.J., Lovering A.L.,
RA   Gabrielsen M.;
RT   "High-resolution structure of the alcohol dehydrogenase domain of the
RT   bifunctional bacterial enzyme AdhE.";
RL   Acta Crystallogr. F Struct. Biol. Commun. 76:414-421(2020).
CC   -!- FUNCTION: Under fermentative conditions, catalyzes the sequential NADH-
CC       dependent reduction of acetyl-CoA to acetaldehyde and then to ethanol
CC       (By similarity). Plays an important role in virulence and is critical
CC       for proper regulation of virulence gene expression (PubMed:24846743).
CC       {ECO:0000250|UniProtKB:P0A9Q7, ECO:0000269|PubMed:24846743}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetaldehyde + CoA + NAD(+) = acetyl-CoA + H(+) + NADH;
CC         Xref=Rhea:RHEA:23288, ChEBI:CHEBI:15343, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945; EC=1.2.1.10;
CC         Evidence={ECO:0000250|UniProtKB:P0A9Q7};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:23290;
CC         Evidence={ECO:0000250|UniProtKB:P0A9Q7};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ethanol + NAD(+) = acetaldehyde + H(+) + NADH;
CC         Xref=Rhea:RHEA:25290, ChEBI:CHEBI:15343, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16236, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1;
CC         Evidence={ECO:0000250|UniProtKB:P0A9Q7};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:25292;
CC         Evidence={ECO:0000250|UniProtKB:P0A9Q7};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a primary alcohol + NAD(+) = an aldehyde + H(+) + NADH;
CC         Xref=Rhea:RHEA:10736, ChEBI:CHEBI:15378, ChEBI:CHEBI:15734,
CC         ChEBI:CHEBI:17478, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1;
CC         Evidence={ECO:0000250|UniProtKB:P0A9Q7};
CC   -!- COFACTOR:
CC       Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC         Evidence={ECO:0000269|PubMed:32880589};
CC   -!- SUBUNIT: Forms long filaments, called spirosomes.
CC       {ECO:0000250|UniProtKB:P0A9Q7}.
CC   -!- DOMAIN: Contains an N-terminal aldehyde dehydrogenase (ALDH) domain and
CC       a C-terminal iron-dependent alcohol dehydrogenase (ADH) domain,
CC       interconnected by a short linker. {ECO:0000250|UniProtKB:P0A9Q7}.
CC   -!- DISRUPTION PHENOTYPE: Deletion of the gene affects gene expression. It
CC       leads to strong expression of non-functional flagella coupled to a
CC       complete lack of the type 3 secretion system (T3SS), including the
CC       structural proteins that comprise the secretory apparatus and its
CC       effector proteins. Mutant displays a 'paralyzed' phenotype. It also
CC       results in excretion of acetate into the surrounding environment, and
CC       reduced binding to host cells, likely because it lacks the T3SS.
CC       Deletion of the gene affects colonization and clinical disease in vivo.
CC       {ECO:0000269|PubMed:24846743}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the aldehyde
CC       dehydrogenase family. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the iron-containing
CC       alcohol dehydrogenase family. {ECO:0000305}.
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DR   EMBL; AE005174; AAG56096.1; -; Genomic_DNA.
DR   EMBL; BA000007; BAB35164.1; -; Genomic_DNA.
DR   PIR; E90846; E90846.
DR   RefSeq; NP_309768.1; NC_002695.1.
DR   RefSeq; WP_000301651.1; NZ_VOAI01000031.1.
DR   PDB; 6SCG; X-ray; 1.65 A; A/B=1-891.
DR   PDB; 6SCI; X-ray; 1.95 A; A/B=1-891.
DR   PDBsum; 6SCG; -.
DR   PDBsum; 6SCI; -.
DR   AlphaFoldDB; P0A9Q8; -.
DR   SASBDB; P0A9Q8; -.
DR   SMR; P0A9Q8; -.
DR   STRING; 155864.Z2016; -.
DR   GeneID; 75203353; -.
DR   GeneID; 913110; -.
DR   KEGG; ece:Z2016; -.
DR   KEGG; ecs:ECs_1741; -.
DR   PATRIC; fig|386585.9.peg.1842; -.
DR   eggNOG; COG1012; Bacteria.
DR   eggNOG; COG1454; Bacteria.
DR   HOGENOM; CLU_007207_2_2_6; -.
DR   OMA; KIMWVLY; -.
DR   Proteomes; UP000000558; Chromosome.
DR   Proteomes; UP000002519; Chromosome.
DR   GO; GO:0008774; F:acetaldehyde dehydrogenase (acetylating) activity; IEA:UniProtKB-EC.
DR   GO; GO:0004022; F:alcohol dehydrogenase (NAD+) activity; IEA:UniProtKB-EC.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0006066; P:alcohol metabolic process; IEA:InterPro.
DR   GO; GO:0015976; P:carbon utilization; IEA:InterPro.
DR   CDD; cd08178; AAD_C; 1.
DR   CDD; cd07081; ALDH_F20_ACDH_EutE-like; 1.
DR   Gene3D; 3.40.50.1970; -; 1.
DR   Gene3D; 1.20.1090.10; Dehydroquinate synthase-like - alpha domain; 1.
DR   InterPro; IPR034789; AAD_C.
DR   InterPro; IPR001670; ADH_Fe/GldA.
DR   InterPro; IPR018211; ADH_Fe_CS.
DR   InterPro; IPR039697; Alcohol_dehydrogenase_Fe.
DR   InterPro; IPR016161; Ald_DH/histidinol_DH.
DR   InterPro; IPR016163; Ald_DH_C.
DR   InterPro; IPR016162; Ald_DH_N.
DR   InterPro; IPR015590; Aldehyde_DH_dom.
DR   InterPro; IPR012079; Bifunc_Ald-ADH.
DR   PANTHER; PTHR11496; ALCOHOL DEHYDROGENASE; 1.
DR   PANTHER; PTHR11496:SF83; HYDROXYACID-OXOACID TRANSHYDROGENASE, MITOCHONDRIAL; 1.
DR   Pfam; PF00171; Aldedh; 1.
DR   Pfam; PF00465; Fe-ADH; 1.
DR   PIRSF; PIRSF000111; ALDH_ADH; 1.
DR   SUPFAM; SSF53720; ALDH-like; 1.
DR   SUPFAM; SSF56796; Dehydroquinate synthase-like; 1.
DR   PROSITE; PS00913; ADH_IRON_1; 1.
DR   PROSITE; PS00060; ADH_IRON_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Iron; Metal-binding; Multifunctional enzyme; NAD;
KW   Oxidoreductase; Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9Q7"
FT   CHAIN           2..891
FT                   /note="Bifunctional aldehyde-alcohol dehydrogenase AdhE"
FT                   /id="PRO_0000087838"
FT   REGION          2..440
FT                   /note="Aldehyde dehydrogenase"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9Q7"
FT   REGION          441..448
FT                   /note="Linker"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9Q7"
FT   REGION          449..891
FT                   /note="Alcohol dehydrogenase"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9Q7"
FT   ACT_SITE        246
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:Q9HTJ1"
FT   BINDING         110..115
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9Q7"
FT   BINDING         195
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9Q7"
FT   BINDING         213
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9Q7"
FT   BINDING         335
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9Q7"
FT   BINDING         419
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9Q7"
FT   BINDING         487
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:32880589,
FT                   ECO:0007744|PDB:6SCG"
FT   BINDING         519
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:32880589,
FT                   ECO:0007744|PDB:6SCG"
FT   BINDING         546..550
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:32880589,
FT                   ECO:0007744|PDB:6SCG"
FT   BINDING         597..598
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:32880589,
FT                   ECO:0007744|PDB:6SCG"
FT   BINDING         610
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9Q7"
FT   BINDING         619
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9Q7"
FT   BINDING         638
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:32880589,
FT                   ECO:0007744|PDB:6SCG"
FT   BINDING         653
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000269|PubMed:32880589,
FT                   ECO:0007744|PDB:6SCG, ECO:0007744|PDB:6SCI"
FT   BINDING         657
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000269|PubMed:32880589,
FT                   ECO:0007744|PDB:6SCG, ECO:0007744|PDB:6SCI"
FT   BINDING         723
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000269|PubMed:32880589,
FT                   ECO:0007744|PDB:6SCG, ECO:0007744|PDB:6SCI"
FT   BINDING         737
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000269|PubMed:32880589,
FT                   ECO:0007744|PDB:6SCG, ECO:0007744|PDB:6SCI"
SQ   SEQUENCE   891 AA;  96127 MW;  75469F57419C8C79 CRC64;
     MAVTNVAELN ALVERVKKAQ REYASFTQEQ VDKIFRAAAL AAADARIPLA KMAVAESGMG
     IVEDKVIKNH FASEYIYNAY KDEKTCGVLS EDDTFGTITI AEPIGIICGI VPTTNPTSTA
     IFKSLISLKT RNAIIFSPHP RAKDATNKAA DIVLQAAIAA GAPKDLIGWI DQPSVELSNA
     LMHHPDINLI LATGGPGMVK AAYSSGKPAI GVGAGNTPVV IDETADIKRA VASVLMSKTF
     DNGVICASEQ SVVVVDSVYD AVRERFATHG GYLLQGKELK AVQDVILKNG ALNAAIVGQP
     AYKIAELAGF SVPENTKILI GEVTVVDESE PFAHEKLSPT LAMYRAKDFE DAVEKAEKLV
     AMGGIGHTSC LYTDQDNQPA RVSYFGQKMK TARILINTPA SQGGIGDLYN FKLAPSLTLG
     CGSWGGNSIS ENVGPKHLIN KKTVAKRAEN MLWHKLPKSI YFRRGSLPIA LDEVITDGHK
     RALIVTDRFL FNNGYADQIT SVLKAAGVET EVFFEVEADP TLSIVRKGAE LANSFKPDVI
     IALGGGSPMD AAKIMWVMYE HPETHFEELA LRFMDIRKRI YKFPKMGVKA KMIAVTTTSG
     TGSEVTPFAV VTDDATGQKY PLADYALTPD MAIVDANLVM DMPKSLCAFG GLDAVTHAME
     AYVSVLASEF SDGQALQALK LLKEYLPASY HEGSKNPVAR ERVHSAATIA GIAFANAFLG
     VCHSMAHKLG SQFHIPHGLA NALLICNVIR YNANDNPTKQ TAFSQYDRPQ ARRRYAEIAD
     HLGLSAPGDR TAAKIEKLLA WLETLKAELG IPKSIREAGV QEADFLANVD KLSEDAFDDQ
     CTGANPRYPL ISELKQILLD TYYGRDYVEG ETAAKKEAAP AKAEKKAKKS A
//