4HBDH_CUPNE
ID 4HBDH_CUPNE Reviewed; 382 AA.
AC Q59104;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=4-hydroxybutyrate dehydrogenase {ECO:0000303|PubMed:7851418};
DE Short=4HbD {ECO:0000250|UniProtKB:P38945};
DE EC=1.1.1.61 {ECO:0000269|PubMed:7851418};
DE AltName: Full=Gamma-hydroxybutyrate dehydrogenase {ECO:0000303|PubMed:31981617};
DE Short=GHBDH {ECO:0000303|PubMed:31981617};
GN Name=gbd {ECO:0000303|PubMed:7851418};
GN ORFNames=I6H87_18265 {ECO:0000312|EMBL:QQB76620.1};
OS Cupriavidus necator (Alcaligenes eutrophus) (Ralstonia eutropha).
OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales;
OC Burkholderiaceae; Cupriavidus.
OX NCBI_TaxID=106590;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=H16 / SK4040;
RX PubMed=7851418; DOI=10.1111/j.1432-1033.1995.tb20358.x;
RA Valentin H.E., Zwingmann G., Schoenebaum A., Steinbuechel A.;
RT "Metabolic pathway for biosynthesis of poly(3-hydroxybutyrate-co-4-
RT hydroxybutyrate) from 4-hydroxybutyrate by Alcaligenes eutrophus.";
RL Eur. J. Biochem. 227:43-60(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=337 / ATCC 17699D-5 / FDAARGOS_1030;
RA Kerrigan L., Long C., Tallon L., Sadzewicz L., Zhao X., Boylan J., Ott S.,
RA Bowen H., Vavikolanu K., Mehta A., Aluvathingal J., Nadendla S., Yan Y.,
RA Sichtig H.;
RT "FDA dAtabase for Regulatory Grade micrObial Sequences (FDA-ARGOS):
RT supporting development and validation of infectious disease Dx tests.";
RL Submitted (DEC-2020) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND MUTAGENESIS OF ASP-193; HIS-197; HIS-261; HIS-265 AND
RP HIS-280.
RX PubMed=31981617; DOI=10.1016/j.bbapap.2020.140376;
RA Taxon E.S., Halbers L.P., Parsons S.M.;
RT "Kinetics aspects of gamma-hydroxybutyrate dehydrogenase.";
RL Biochim. Biophys. Acta 1868:140376-140376(2020).
CC -!- FUNCTION: Involved in the degradation of 4-hydroxybutyrate
CC (PubMed:7851418). Catalyzes the interconversion of gamma-
CC hydroxybutyrate (GHB) and succinic semialdehyde (SSA)
CC (PubMed:31981617). {ECO:0000269|PubMed:31981617,
CC ECO:0000269|PubMed:7851418}.
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;
CC Evidence={ECO:0000269|PubMed:31981617};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:P0A9S1};
CC -!- ACTIVITY REGULATION: Shows competitive inhibition of GHBDH activity by
CC the product succinic semialdehyde, and non-competitive inhibitions by
CC the three other substrate-product combinations. The conversion of GHB
CC to SSA is activated by two different saturating purified nudix
CC hydrolases, B.methanolicus activator ACT and E.coli NudF. The nudix
CC hydrolases do not activate the reverse reaction.
CC {ECO:0000269|PubMed:31981617}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.98 mM for 4-hydroxybutanoate {ECO:0000269|PubMed:31981617};
CC KM=0.064 mM for NAD(+) {ECO:0000269|PubMed:31981617};
CC Note=kcat is 8.4 sec(-1) with 4-hydroxybutanoate as substrate. kcat
CC is 8.9 sec(-1) with NAD(+) as substrate.
CC {ECO:0000269|PubMed:31981617};
CC pH dependence:
CC Optimum pH is 9.0. {ECO:0000269|PubMed:31981617};
CC -!- SIMILARITY: Belongs to the iron-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; L36817; AAC41425.1; -; Genomic_DNA.
DR EMBL; CP066018; QQB76620.1; -; Genomic_DNA.
DR PIR; I39568; I39568.
DR RefSeq; WP_010810019.1; NZ_LVWN01000023.1.
DR SMR; Q59104; -.
DR GeneID; 57643652; -.
DR BRENDA; 1.1.1.61; 231.
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; PS00913; ADH_IRON_1; 1.
PE 1: Evidence at protein level;
KW Iron; Metal-binding; NAD; Nucleotide-binding; Oxidoreductase.
FT CHAIN 1..382
FT /note="4-hydroxybutyrate dehydrogenase"
FT /id="PRO_0000454377"
FT BINDING 37
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT BINDING 67
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT BINDING 94..98
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT BINDING 138..142
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT BINDING 159
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT BINDING 193
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT BINDING 197
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT BINDING 261
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT BINDING 280
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT BINDING 280
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P0A9S1"
FT MUTAGEN 193
FT /note="D->A: Retains very low activity."
FT /evidence="ECO:0000269|PubMed:31981617"
FT MUTAGEN 197
FT /note="H->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:31981617"
FT MUTAGEN 261
FT /note="H->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:31981617"
FT MUTAGEN 265
FT /note="H->A: 75% decrease in Vmax. Optimum pH is 9.5."
FT /evidence="ECO:0000269|PubMed:31981617"
FT MUTAGEN 265
FT /note="H->C: 95% decrease in Vmax. Optimum pH is 8.5."
FT /evidence="ECO:0000269|PubMed:31981617"
FT MUTAGEN 265
FT /note="H->D: Retains very low activity."
FT /evidence="ECO:0000269|PubMed:31981617"
FT MUTAGEN 265
FT /note="H->Y: Loss of activity."
FT /evidence="ECO:0000269|PubMed:31981617"
FT MUTAGEN 280
FT /note="H->A: Retains very low activity."
FT /evidence="ECO:0000269|PubMed:31981617"
SQ SEQUENCE 382 AA; 40495 MW; BB8588BE078E69EA CRC64;
MAFIYYLTHI HLDFGAVSLL KSECERIGIR RPLLVTDKGV VAAGVAQRAI DAMQGLQVAV
FDETPSNPTE AMVRKAAAQY REAGCDGLVA VGGGSSIDLA KGIAILATHE GELTTYATIE
GGSARITDKA APLIAVPTTS GTGSEVARGA IIILDDGRKL GFHSWHLLPK SAVCDPELTL
GLPAGLTAAT GMDAIAHCIE TFLAPAFNPP ADGIALDGLE RGWGHIERAT RDGQDRDARL
NMMSASMQGA MAFQKGLGCV HSLSHPLGGL KIDGRTGLHH GTLNAVVMPA VLRFNADAPT
VVRDDRYARL RRAMHLPDGA DIAQAVHDMT VRLGLPTGLR QMGVTEDMFD KVIAGALVDH
CHKTNPKEAS AADYRRMLEQ SM
