HDHA_BACFN
ID HDHA_BACFN Reviewed; 259 AA.
AC Q5LA59;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=7alpha-hydroxysteroid dehydrogenase {ECO:0000303|PubMed:14756531};
DE Short=7alpha-HSDH {ECO:0000303|PubMed:14756531};
DE EC=1.1.1.159 {ECO:0000269|PubMed:14756531};
DE AltName: Full=Aromatic aldehyde reductase {ECO:0000305|PubMed:21600233};
DE EC=1.1.1.- {ECO:0000269|PubMed:21600233};
DE AltName: Full=NAD-dependent 7alpha-hydroxysteroid dehydrogenase {ECO:0000303|PubMed:14756531};
GN Name=hdhA {ECO:0000312|EMBL:CAH09015.1};
GN ORFNames=BF9343_3234 {ECO:0000312|EMBL:CAH09015.1};
OS Bacteroides fragilis (strain ATCC 25285 / DSM 2151 / CCUG 4856 / JCM 11019
OS / NCTC 9343 / Onslow).
OC Bacteria; Bacteroidetes; Bacteroidia; Bacteroidales; Bacteroidaceae;
OC Bacteroides.
OX NCBI_TaxID=272559;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-23, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY,
RP SUBUNIT, AND INDUCTION.
RC STRAIN=ATCC 25285 / DSM 2151 / CCUG 4856 / JCM 11019 / NCTC 9343 / Onslow;
RX PubMed=14756531; DOI=10.1007/s00284-003-4079-4;
RA Bennett M.J., McKnight S.L., Coleman J.P.;
RT "Cloning and characterization of the NAD-dependent 7alpha-Hydroxysteroid
RT dehydrogenase from Bacteroides fragilis.";
RL Curr. Microbiol. 47:475-484(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25285 / DSM 2151 / CCUG 4856 / JCM 11019 / NCTC 9343 / Onslow;
RX PubMed=15746427; DOI=10.1126/science.1107008;
RA Cerdeno-Tarraga A.-M., Patrick S., Crossman L.C., Blakely G., Abratt V.,
RA Lennard N., Poxton I., Duerden B., Harris B., Quail M.A., Barron A.,
RA Clark L., Corton C., Doggett J., Holden M.T.G., Larke N., Line A., Lord A.,
RA Norbertczak H., Ormond D., Price C., Rabbinowitsch E., Woodward J.,
RA Barrell B.G., Parkhill J.;
RT "Extensive DNA inversions in the B. fragilis genome control variable gene
RT expression.";
RL Science 307:1463-1465(2005).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=21600233; DOI=10.1016/j.steroids.2011.05.001;
RA Liu Y., Lv T., Ren J., Wang M., Wu Q., Zhu D.;
RT "The catalytic promiscuity of a microbial 7alpha-hydroxysteroid
RT dehydrogenase. Reduction of non-steroidal carbonyl compounds.";
RL Steroids 76:1136-1140(2011).
CC -!- FUNCTION: 7alpha-hydroxysteroid dehydrogenase involved in the
CC metabolism of bile acids in the gut. Catalyzes the NAD(+)-dependent
CC oxidation of the 7alpha-hydroxy group of 7alpha-hydroxysteroids, such
CC as cholate, chenodeoxycholate, taurochenodeoxycholate,
CC glycochenodeoxycholate, taurocholate and glycocholate, to the
CC corresponding 7-oxosteroids (PubMed:14756531). Since it is also able to
CC catalyze the reduction of nonsteroidal carbonyl compounds such as
CC various benzaldehyde analogs to their corresponding benzyl alcohols,
CC this enzyme may also function in the detoxification of xenobiotics
CC containing carbonyl groups in the large intestine (PubMed:21600233).
CC {ECO:0000269|PubMed:14756531, ECO:0000269|PubMed:21600233}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholate + NAD(+) = 3alpha,12alpha-dihydroxy-7-oxo-5beta-
CC cholanate + H(+) + NADH; Xref=Rhea:RHEA:19409, ChEBI:CHEBI:11893,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29747, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.1.1.159;
CC Evidence={ECO:0000269|PubMed:14756531};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19410;
CC Evidence={ECO:0000305|PubMed:14756531};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chenodeoxycholate + NAD(+) = 7-oxolithocholate + H(+) + NADH;
CC Xref=Rhea:RHEA:42036, ChEBI:CHEBI:15378, ChEBI:CHEBI:36234,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78605;
CC Evidence={ECO:0000269|PubMed:14756531};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42037;
CC Evidence={ECO:0000305|PubMed:14756531};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + taurochenodeoxycholate = 7-oxotaurolithocholate +
CC H(+) + NADH; Xref=Rhea:RHEA:53824, ChEBI:CHEBI:9407,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:137724; Evidence={ECO:0000269|PubMed:14756531};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53825;
CC Evidence={ECO:0000305|PubMed:14756531};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycochenodeoxycholate + NAD(+) = 7-oxoglycolithocholate +
CC H(+) + NADH; Xref=Rhea:RHEA:53844, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:36252, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:137818; Evidence={ECO:0000269|PubMed:14756531};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53845;
CC Evidence={ECO:0000305|PubMed:14756531};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + taurocholate = 7-oxo-taurodeoxycholate + H(+) + NADH;
CC Xref=Rhea:RHEA:53848, ChEBI:CHEBI:15378, ChEBI:CHEBI:36257,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:137820;
CC Evidence={ECO:0000269|PubMed:14756531};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53849;
CC Evidence={ECO:0000305|PubMed:14756531};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycocholate + NAD(+) = 7-oxo-glycodeoxycholate + H(+) + NADH;
CC Xref=Rhea:RHEA:53852, ChEBI:CHEBI:15378, ChEBI:CHEBI:29746,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:137824;
CC Evidence={ECO:0000269|PubMed:14756531};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53853;
CC Evidence={ECO:0000305|PubMed:14756531};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an aromatic primary alcohol + NAD(+) = an aromatic aldehyde +
CC H(+) + NADH; Xref=Rhea:RHEA:12076, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33855, ChEBI:CHEBI:33857, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:21600233};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=benzyl alcohol + NAD(+) = benzaldehyde + H(+) + NADH;
CC Xref=Rhea:RHEA:64696, ChEBI:CHEBI:15378, ChEBI:CHEBI:17169,
CC ChEBI:CHEBI:17987, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:21600233};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-cyanobenzyl alcohol + NAD(+) = 4-cyanobenzaldehyde + H(+) +
CC NADH; Xref=Rhea:RHEA:65044, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:156307, ChEBI:CHEBI:156308;
CC Evidence={ECO:0000269|PubMed:21600233};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-acetoxybenzyl alcohol + NAD(+) = 4-acetoxybenzaldehyde +
CC H(+) + NADH; Xref=Rhea:RHEA:65048, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:86559,
CC ChEBI:CHEBI:156306; Evidence={ECO:0000269|PubMed:21600233};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-(trifluoromethyl)benzyl alcohol + NAD(+) = 4-
CC (trifluoromethyl)benzaldehyde + H(+) + NADH; Xref=Rhea:RHEA:65052,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:156309, ChEBI:CHEBI:156310;
CC Evidence={ECO:0000269|PubMed:21600233};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.177 mM for cholate (at pH 8.5) {ECO:0000269|PubMed:14756531};
CC KM=0.024 mM for chenodeoxycholate (at pH 8.5)
CC {ECO:0000269|PubMed:14756531};
CC KM=0.231 mM for glycocholate (at pH 8.5)
CC {ECO:0000269|PubMed:14756531};
CC KM=0.054 mM for glycochenodeoxycholate (at pH 8.5)
CC {ECO:0000269|PubMed:14756531};
CC KM=0.119 mM for taurocholate (at pH 8.5)
CC {ECO:0000269|PubMed:14756531};
CC KM=0.024 mM for taurochenodeoxycholate (at pH 8.5)
CC {ECO:0000269|PubMed:14756531};
CC KM=0.524 mM for 3alpha,12alpha-dihydroxy-7-oxo-5beta-cholanate (at pH
CC 6.5) {ECO:0000269|PubMed:14756531};
CC KM=0.212 mM for NAD(+) (in the presence of cholate, at pH 8.5)
CC {ECO:0000269|PubMed:14756531};
CC KM=0.709 mM for NAD(+) (in the presence of chenodeoxycholate, at pH
CC 8.5) {ECO:0000269|PubMed:14756531};
CC KM=0.020 mM for NADH (in the presence of 3alpha,12alpha-dihydroxy-7-
CC oxo-5beta-cholanate, at pH 8.5) {ECO:0000269|PubMed:14756531};
CC Vmax=957 umol/min/mg enzyme for the oxidation of cholate (at pH 8.5)
CC {ECO:0000269|PubMed:14756531};
CC Vmax=906 umol/min/mg enzyme for the oxidation of chenodeoxycholate
CC (at pH 8.5) {ECO:0000269|PubMed:14756531};
CC Vmax=648 umol/min/mg enzyme for the oxidation of glycocholate (at pH
CC 8.5) {ECO:0000269|PubMed:14756531};
CC Vmax=1116 umol/min/mg enzyme for the oxidation of
CC glycochenodeoxycholate (at pH 8.5) {ECO:0000269|PubMed:14756531};
CC Vmax=798 umol/min/mg enzyme for the oxidation of taurocholate (at pH
CC 8.5) {ECO:0000269|PubMed:14756531};
CC Vmax=1050 umol/min/mg enzyme for the oxidation of
CC taurochenodeoxycholate (at pH 8.5) {ECO:0000269|PubMed:14756531};
CC Vmax=53 umol/min/mg enzyme for the reduction of 3alpha,12alpha-
CC dihydroxy-7-oxo-5beta-cholanate (at pH 6.5)
CC {ECO:0000269|PubMed:14756531};
CC pH dependence:
CC Optimum pH is pH 8.5 (NAD reduction, bile acid oxidation) and 6.5
CC (NADH oxidation, bile acid reduction). {ECO:0000269|PubMed:14756531};
CC Temperature dependence:
CC Is relatively thermostable, retaining 95% of initial activity after 1
CC hour at 65 degrees Celsius. {ECO:0000269|PubMed:14756531};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:14756531}.
CC -!- INDUCTION: Up-regulated by cholate and after the transition of the
CC cells from log phase to stationary growth phase.
CC {ECO:0000269|PubMed:14756531}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AF173833; AAD49430.2; -; Genomic_DNA.
DR EMBL; CR626927; CAH09015.1; -; Genomic_DNA.
DR RefSeq; WP_008657214.1; NC_003228.3.
DR AlphaFoldDB; Q5LA59; -.
DR SMR; Q5LA59; -.
DR STRING; 272559.BF9343_3234; -.
DR SwissLipids; SLP:000001981; -.
DR EnsemblBacteria; CAH09015; CAH09015; BF9343_3234.
DR KEGG; bfs:BF9343_3234; -.
DR eggNOG; COG1028; Bacteria.
DR HOGENOM; CLU_010194_1_0_10; -.
DR OMA; GICEFKE; -.
DR OrthoDB; 1356861at2; -.
DR BioCyc; BFRA272559:G1GHZ-3529-MON; -.
DR SABIO-RK; Q5LA59; -.
DR Proteomes; UP000006731; Chromosome.
DR GO; GO:0008709; F:cholate 7-alpha-dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0030573; P:bile acid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Bile acid catabolism; Direct protein sequencing; Lipid degradation;
KW Lipid metabolism; NAD; Oxidoreductase; Reference proteome;
KW Steroid metabolism.
FT CHAIN 1..259
FT /note="7alpha-hydroxysteroid dehydrogenase"
FT /id="PRO_0000451448"
FT ACT_SITE 158
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P0AET8"
FT BINDING 18
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P0AET8"
FT BINDING 37..38
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P0AET8"
FT BINDING 90
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P0AET8"
FT BINDING 145
FT /ligand="glycochenodeoxycholate"
FT /ligand_id="ChEBI:CHEBI:36252"
FT /evidence="ECO:0000250|UniProtKB:P0AET8"
FT BINDING 158
FT /ligand="glycochenodeoxycholate"
FT /ligand_id="ChEBI:CHEBI:36252"
FT /evidence="ECO:0000250|UniProtKB:P0AET8"
FT BINDING 158
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P0AET8"
FT BINDING 162
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P0AET8"
FT BINDING 191..193
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P0AET8"
FT SITE 145
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P0AET8"
FT SITE 162
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250|UniProtKB:P0AET8"
SQ SEQUENCE 259 AA; 27662 MW; 1970D3592B871EDB CRC64;
MNRFENKIII ITGAAGGIGA STTRRIVSEG GKVVIADYSR EKADQFAAEL SNSGADVRPV
YFSATELKSC KELITFTMKE YGQIDVLVNN VGGTNPRRDT NIETLDMDYF DEAFHLNLSC
TMYLSQLVIP IMSTQGGGNI VNVASISGIT ADSNGTLYGA SKAGVINLTK YIATQTGKKN
IRCNAVAPGL ILTPAALNNL NEEVRKIFLG QCATPYLGEP QDVAATIAFL ASEDARYITG
QTIVVDGGLT IHNPTINLV
