4HBDH_CLOK5
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 03-AUG-2022, entry version 93.
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; Firmicutes; 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 EnsemblBacteria; EDK35022; EDK35022; CKL_3014.
DR KEGG; ckl:CKL_3014; -.
DR eggNOG; COG1454; Bacteria.
DR HOGENOM; CLU_007207_0_0_9; -.
DR OMA; FHVAHGE; -.
DR OrthoDB; 1456634at2; -.
DR BioCyc; MetaCyc:MON-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 InterPro; IPR001670; ADH_Fe/GldA.
DR InterPro; IPR018211; ADH_Fe_CS.
DR InterPro; IPR039697; Alcohol_dehydrogenase_Fe.
DR PANTHER; PTHR11496; PTHR11496; 1.
DR Pfam; PF00465; Fe-ADH; 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
