HSDHB_RUMGV
ID HSDHB_RUMGV Reviewed; 263 AA.
AC A7B4V1;
DT 12-SEP-2018, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 1.
DT 03-AUG-2022, entry version 64.
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:0000305|PubMed:23729502};
DE AltName: Full=NADP-dependent 7beta-hydroxysteroid dehydrogenase {ECO:0000303|PubMed:23729502};
GN ORFNames=RUMGNA_02585 {ECO:0000312|EMBL:EDN76974.1};
OS Ruminococcus gnavus (strain ATCC 29149 / VPI C7-9).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Lachnospiraceae;
OC Mediterraneibacter.
OX NCBI_TaxID=411470;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 29149 / VPI C7-9;
RA Fulton L., Clifton S., Fulton B., Xu J., Minx P., Pepin K.H., Johnson M.,
RA Thiruvilangam P., Bhonagiri V., Nash W.E., Mardis E.R., Wilson R.K.;
RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 29149 / VPI C7-9;
RA Sudarsanam P., Ley R., Guruge J., Turnbaugh P.J., Mahowald M., Liep D.,
RA Gordon J.;
RT "Draft genome sequence of Ruminococcus gnavus (ATCC 29149).";
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 29149 / VPI C7-9;
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. {ECO:0000305|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:0000305|PubMed:23729502};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20235;
CC Evidence={ECO:0000305|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:0000305|PubMed:23729502};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47541;
CC Evidence={ECO:0000305|PubMed:23729502};
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AAYG02000020; EDN76974.1; -; Genomic_DNA.
DR RefSeq; WP_004843516.1; NZ_PUEL01000004.1.
DR AlphaFoldDB; A7B4V1; -.
DR SMR; A7B4V1; -.
DR STRING; 411470.RUMGNA_02585; -.
DR PRIDE; A7B4V1; -.
DR EnsemblBacteria; EDN76974; EDN76974; RUMGNA_02585.
DR GeneID; 57433518; -.
DR eggNOG; COG0300; Bacteria.
DR BioCyc; MetaCyc:MON-19021; -.
DR BRENDA; 1.1.1.201; 5479.
DR Proteomes; UP000004410; Unassembled WGS sequence.
DR GO; GO:0047022; F:7-beta-hydroxysteroid dehydrogenase (NADP+) activity; IEA:UniProtKB-EC.
DR GO; GO:0051287; F:NAD binding; ISS:UniProtKB.
DR GO; GO:0033764; F:steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IDA:UniProtKB.
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; Lipid degradation; Lipid metabolism; NADP;
KW Nucleotide-binding; Oxidoreductase; Steroid metabolism.
FT CHAIN 1..263
FT /note="7beta-hydroxysteroid dehydrogenase"
FT /id="PRO_0000444979"
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
