HSDHB_RUMGN
ID HSDHB_RUMGN Reviewed; 263 AA.
AC R9UAM1;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 1.
DT 03-AUG-2022, entry version 47.
DE RecName: Full=7beta-hydroxysteroid dehydrogenase {ECO:0000303|PubMed:23729502};
DE Short=7beta-HSDH {ECO:0000303|PubMed:23729502};
DE EC=1.1.1.201 {ECO:0000269|PubMed:23729502};
DE AltName: Full=NADP-dependent 7beta-hydroxysteroid dehydrogenase {ECO:0000303|PubMed:23729502};
OS Ruminococcus gnavus.
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Lachnospiraceae;
OC Mediterraneibacter.
OX NCBI_TaxID=33038 {ECO:0000312|EMBL:AGN52919.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-20, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBSTRATE
RP SPECIFICITY.
RC STRAIN=N53;
RX PubMed=23729502; DOI=10.1194/jlr.m039834;
RA Lee J.Y., Arai H., Nakamura Y., Fukiya S., Wada M., Yokota A.;
RT "Contribution of the 7beta-hydroxysteroid dehydrogenase from Ruminococcus
RT gnavus N53 to ursodeoxycholic acid formation in the human colon.";
RL J. Lipid Res. 54:3062-3069(2013).
CC -!- FUNCTION: 7beta-hydroxysteroid dehydrogenase that catalyzes the
CC reduction of the 7-oxo group of 7-oxo-lithocholate (7-oxo-LCA), to
CC yield ursodeoxycholate (UDCA). As R.gnavus is a common core bacterium
CC of the human gut microbiota, this enzyme contributes to the formation
CC of UDCA in the human colon. UDCA is regarded as a chemopreventive
CC beneficial secondary bile acid due to its low hydrophobicity; it
CC protects hepatocytes and bile duct epithelial cells against necrosis
CC and apoptosis induced by more hydrophobic secondary bile acids like
CC deoxycholate (DCA). This enzyme is also able to catalyze the reverse
CC reaction in vitro, i.e. the oxidation of the 7beta-hydroxy group of
CC UDCA to 7-oxo-LCA, but much less efficiently than the reduction
CC reaction, and this oxidation reaction is not observed in vivo. It is
CC specific for NADPH/NADP(+) as the electron acceptor/donor since the
CC activity observed with NADH/NAD(+) is less than 0.5% of that assayed
CC using NADPH/NADP(+) in both directions. {ECO:0000269|PubMed:23729502}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 7beta-hydroxysteroid + NADP(+) = a 7-oxosteroid + H(+) +
CC NADPH; Xref=Rhea:RHEA:20233, ChEBI:CHEBI:15378, ChEBI:CHEBI:35349,
CC ChEBI:CHEBI:47789, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.201; Evidence={ECO:0000269|PubMed:23729502};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20235;
CC Evidence={ECO:0000269|PubMed:23729502};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7-oxolithocholate + H(+) + NADPH = NADP(+) + ursodeoxycholate;
CC Xref=Rhea:RHEA:47540, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78604, ChEBI:CHEBI:78605;
CC Evidence={ECO:0000269|PubMed:23729502};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47541;
CC Evidence={ECO:0000269|PubMed:23729502};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=38.8 uM for 7-oxolithocholate (7-oxo-LCA) (at pH 6 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:23729502};
CC KM=974 uM for ursodeoxycholate (UDCA) (at pH 10 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:23729502};
CC Vmax=23.8 umol/min/mg enzyme for the reduction of 7-oxolithocholate
CC (7-oxo-LCA) (at pH 6 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:23729502};
CC Vmax=11.1 umol/min/mg enzyme for the oxidation of ursodeoxycholate
CC (UDCA) (at pH 10 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:23729502};
CC Note=kcat is 700 min(-1) for the reduction of 7-oxolithocholate (7-
CC oxo-LCA) (at pH 6 and 37 degrees Celsius). kcat is 326 min(-1) for
CC the oxidation of ursodeoxycholate (UDCA) (at pH 10 and 37 degrees
CC Celsius). {ECO:0000269|PubMed:23729502};
CC pH dependence:
CC Optimum pH is 6 and 10 for the reduction and oxidation reactions,
CC respectively. {ECO:0000269|PubMed:23729502};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius for the reduction reaction.
CC The enzyme appears mostly inactivated at 60 degrees Celsius.
CC {ECO:0000269|PubMed:23729502};
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; KF052988; AGN52919.1; -; Genomic_DNA.
DR RefSeq; WP_004843516.1; NZ_QSPZ01000009.1.
DR AlphaFoldDB; R9UAM1; -.
DR SMR; R9UAM1; -.
DR STRING; 33038.GCA_900067245_02691; -.
DR SwissLipids; SLP:000001345; -.
DR EnsemblBacteria; PLT60181; PLT60181; CDL27_06180.
DR EnsemblBacteria; PLT69421; PLT69421; CDL25_06720.
DR EnsemblBacteria; RGK06386; RGK06386; DXD36_06990.
DR EnsemblBacteria; RGM25872; RGM25872; DXC31_01535.
DR EnsemblBacteria; RHM39316; RHM39316; DWZ70_05020.
DR GeneID; 57433518; -.
DR KEGG; ag:AGN52919; -.
DR GO; GO:0047022; F:7-beta-hydroxysteroid dehydrogenase (NADP+) activity; IEA:UniProtKB-EC.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
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 Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Bile acid catabolism; Direct protein sequencing; Lipid degradation;
KW Lipid metabolism; NADP; Nucleotide-binding; Oxidoreductase;
KW Steroid metabolism.
FT CHAIN 1..263
FT /note="7beta-hydroxysteroid dehydrogenase"
FT /id="PRO_0000450343"
FT ACT_SITE 156
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:A4ECA9"
FT BINDING 17..21
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:A4ECA9"
FT BINDING 40..41
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:A4ECA9"
FT BINDING 66..67
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:A4ECA9"
FT BINDING 240
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:A4ECA9"
FT SITE 143
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:A4ECA9"
FT SITE 160
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250|UniProtKB:P0AET8"
SQ SEQUENCE 263 AA; 29289 MW; B4E17355A93846D7 CRC64;
MTLREKYGEW GIILGATEGV GKAFCERLAK EGMNVVMVGR REEKLKELGE ELKNTYEIDY
KVVKADFSLP DATDKIFAAT ENLDMGFMAY VACLHSFGKI QDTPWEKHEA MINVNVVTFM
KCFYHYMKIF AAQDRGAVIN VSSMTGISSS PWNGQYGAGK AFILKMTEAV ACETEKTNVD
VEVITLGTTL TPSLLSNLPG GPQGEAVMKT AQTPEEVVDE AFEKLGKELS VISGERNKAS
VHDWKANHTE DDYIRYMGSF YQE
