ID   4HBDH_CLOK5             Reviewed;         371 AA.
AC   P38945; A5N1M6;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   27-MAR-2024, entry version 99.
DE   RecName: Full=4-hydroxybutyrate dehydrogenase {ECO:0000303|PubMed:8328804, ECO:0000303|PubMed:8444151};
DE            Short=4HbD {ECO:0000303|PubMed:8550525};
DE            EC=1.1.1.61 {ECO:0000269|PubMed:7606170, ECO:0000269|PubMed:8328804};
DE   AltName: Full=Gamma-hydroxybutyrate dehydrogenase {ECO:0000250|UniProtKB:Q59104};
DE            Short=GHBDH {ECO:0000250|UniProtKB:Q59104};
DE   AltName: Full=NAD(+)-dependent 4-hydroxybutyrate dehydrogenase {ECO:0000303|PubMed:8444151};
GN   Name=4hbD {ECO:0000303|PubMed:8550525}; OrderedLocusNames=CKL_3014;
OS   Clostridium kluyveri (strain ATCC 8527 / DSM 555 / NCIMB 10680).
OC   Bacteria; Bacillota; Clostridia; Eubacteriales; Clostridiaceae;
OC   Clostridium.
OX   NCBI_TaxID=431943;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP   INDUCTION.
RC   STRAIN=ATCC 8527 / DSM 555 / NCIMB 10680;
RX   PubMed=8550525; DOI=10.1128/jb.178.3.871-880.1996;
RA   Soehling B., Gottschalk G.;
RT   "Molecular analysis of the anaerobic succinate degradation pathway in
RT   Clostridium kluyveri.";
RL   J. Bacteriol. 178:871-880(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 8527 / DSM 555 / NCIMB 10680;
RX   PubMed=18218779; DOI=10.1073/pnas.0711093105;
RA   Seedorf H., Fricke W.F., Veith B., Brueggemann H., Liesegang H.,
RA   Strittmatter A., Miethke M., Buckel W., Hinderberger J., Li F.,
RA   Hagemeier C., Thauer R.K., Gottschalk G.;
RT   "The genome of Clostridium kluyveri, a strict anaerobe with unique
RT   metabolic features.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:2128-2133(2008).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION.
RC   STRAIN=ATCC 8527 / DSM 555 / NCIMB 10680;
RX   PubMed=8328804; DOI=10.1128/aem.59.6.1876-1882.1993;
RA   Wolff R.A., Urben G.W., O'Herrin S.M., Kenealy W.R.;
RT   "Dehydrogenases involved in the conversion of succinate to 4-
RT   hydroxybutanoate by Clostridium kluyveri.";
RL   Appl. Environ. Microbiol. 59:1876-1882(1993).
RN   [4]
RP   FUNCTION.
RC   STRAIN=ATCC 8527 / DSM 555 / NCIMB 10680;
RX   PubMed=8444151; DOI=10.1111/j.1432-1033.1993.tb17641.x;
RA   Soehling B., Gottschalk G.;
RT   "Purification and characterization of a coenzyme-A-dependent succinate-
RT   semialdehyde dehydrogenase from Clostridium kluyveri.";
RL   Eur. J. Biochem. 212:121-127(1993).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP   BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND INDUCTION.
RC   STRAIN=ATCC 8527 / DSM 555 / NCIMB 10680;
RX   PubMed=7606170; DOI=10.1006/prep.1995.1026;
RA   Wolff R.A., Kenealy W.R.;
RT   "Purification and characterization of the oxygen-sensitive 4-
RT   hydroxybutanoate dehydrogenase from Clostridium kluyveri.";
RL   Protein Expr. Purif. 6:206-212(1995).
CC   -!- FUNCTION: Involved in the anaerobic succinate degradation pathway
CC       (PubMed:8328804, PubMed:8444151, PubMed:8550525). Catalyzes the
CC       interconversion of gamma-hydroxybutyrate (GHB) and succinic
CC       semialdehyde (SSA) (PubMed:8328804, PubMed:7606170, PubMed:8550525).
CC       {ECO:0000269|PubMed:7606170, ECO:0000269|PubMed:8328804,
CC       ECO:0000269|PubMed:8444151, ECO:0000269|PubMed:8550525}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4-hydroxybutanoate + NAD(+) = H(+) + NADH + succinate
CC         semialdehyde; Xref=Rhea:RHEA:23948, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16724, ChEBI:CHEBI:57540, ChEBI:CHEBI:57706,
CC         ChEBI:CHEBI:57945; EC=1.1.1.61; Evidence={ECO:0000269|PubMed:7606170,
CC         ECO:0000269|PubMed:8328804, ECO:0000269|PubMed:8550525};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:23950;
CC         Evidence={ECO:0000269|PubMed:7606170, ECO:0000269|PubMed:8328804,
CC         ECO:0000269|PubMed:8550525};
CC   -!- COFACTOR:
CC       Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC         Evidence={ECO:0000269|PubMed:7606170};
CC       Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:7606170};
CC   -!- COFACTOR:
CC       Name=Cu(2+); Xref=ChEBI:CHEBI:29036;
CC         Evidence={ECO:0000269|PubMed:7606170};
CC       Note=Binds 2 Cu(2+) ions per subunit. {ECO:0000269|PubMed:7606170};
CC   -!- ACTIVITY REGULATION: Inactivated by oxygen.
CC       {ECO:0000269|PubMed:7606170}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.56 mM for succinic semialdehyde {ECO:0000269|PubMed:7606170};
CC         KM=0.15 mM for NADH {ECO:0000269|PubMed:7606170};
CC         KM=55 mM for 4-hydroxybutanoate {ECO:0000269|PubMed:7606170};
CC         KM=0.67 mM for NAD {ECO:0000269|PubMed:7606170};
CC       pH dependence:
CC         Optimum pH is 6.1 for the reduction of succinic semialdehyde and pH
CC         9.4 for the oxidation of 4-hydroxybutanoate.
CC         {ECO:0000269|PubMed:7606170};
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:7606170}.
CC   -!- INDUCTION: Induced by growth on ethanol plus succinate.
CC       {ECO:0000269|PubMed:7606170, ECO:0000269|PubMed:8328804,
CC       ECO:0000269|PubMed:8550525}.
CC   -!- SIMILARITY: Belongs to the iron-containing alcohol dehydrogenase
CC       family. {ECO:0000305}.
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DR   EMBL; L21902; AAA92348.1; -; Genomic_DNA.
DR   EMBL; CP000673; EDK35022.1; -; Genomic_DNA.
DR   RefSeq; WP_012103357.1; NC_009706.1.
DR   AlphaFoldDB; P38945; -.
DR   SMR; P38945; -.
DR   STRING; 431943.CKL_3014; -.
DR   KEGG; ckl:CKL_3014; -.
DR   eggNOG; COG1454; Bacteria.
DR   HOGENOM; CLU_007207_0_0_9; -.
DR   BioCyc; MetaCyc:MONOMER-13466; -.
DR   Proteomes; UP000002411; Chromosome.
DR   GO; GO:0047577; F:4-hydroxybutyrate dehydrogenase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR   CDD; cd14860; 4HBD_NAD; 1.
DR   Gene3D; 3.40.50.1970; -; 1.
DR   Gene3D; 1.20.1090.10; Dehydroquinate synthase-like - alpha domain; 1.
DR   InterPro; IPR001670; ADH_Fe/GldA.
DR   InterPro; IPR018211; ADH_Fe_CS.
DR   InterPro; IPR039697; Alcohol_dehydrogenase_Fe.
DR   PANTHER; PTHR11496; ALCOHOL DEHYDROGENASE; 1.
DR   PANTHER; PTHR11496:SF83; HYDROXYACID-OXOACID TRANSHYDROGENASE, MITOCHONDRIAL; 1.
DR   Pfam; PF00465; Fe-ADH; 1.
DR   SUPFAM; SSF56796; Dehydroquinate synthase-like; 1.
DR   PROSITE; PS00060; ADH_IRON_2; 1.
PE   1: Evidence at protein level;
KW   Copper; Iron; Metal-binding; NAD; Nucleotide-binding; Oxidoreductase;
KW   Reference proteome.
FT   CHAIN           1..371
FT                   /note="4-hydroxybutyrate dehydrogenase"
FT                   /id="PRO_0000087840"
FT   BINDING         88..92
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT   BINDING         126..130
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT   BINDING         148
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT   BINDING         182
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT   BINDING         186
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT   BINDING         253
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT   BINDING         267
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT   BINDING         267
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P0A9S1"
SQ   SEQUENCE   371 AA;  41756 MW;  8D4A8DCD94E252C4 CRC64;
     MKLLKLAPDV YKFDTAEEFM KYFKVGKGDF ILTNEFLYKP FLEKFNDGAD AVFQEKYGLG
     EPSDEMINNI IKDIGDKQYN RIIAVGGGSV IDIAKILSLK YTDDSLDLFE GKVPLVKNKE
     LIIVPTTCGT GSEVTNVSVA ELKRRHTKKG IASDELYATY AVLVPEFIKG LPYKFFVTSS
     VDALIHATEA YVSPNANPYT DMFSVKAMEL ILNGYMQMVE KGNDYRVEII EDFVIGSNYA
     GIAFGNAGVG AVHALSYPIG GNYHVPHGEA NYLFFTEIFK TYYEKNPNGK IKDVNKLLAG
     ILKCDESEAY DSLSQLLDKL LSRKPLREYG MKEEEIETFA DSVIEGQQRL LVNNYEPFSR
     EDIVNTYKKL Y
//