3BHDP_RUMGV
ID 3BHDP_RUMGV Reviewed; 276 AA.
AC A7AZH2;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=3beta-hydroxysteroid dehydrogenase {ECO:0000303|PubMed:26192599};
DE Short=3beta-HSDH {ECO:0000303|PubMed:26192599};
DE EC=1.1.1.- {ECO:0000269|PubMed:26192599};
DE AltName: Full=3beta-hydroxycholanate 3-dehydrogenase (NADP(+));
DE EC=1.1.1.393 {ECO:0000269|PubMed:26192599};
DE AltName: Full=NADP-dependent bile acid 3beta-dehydrogenase {ECO:0000305};
GN ORFNames=RUMGNA_00694 {ECO:0000312|EMBL:EDN78833.1};
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 {ECO:0000312|EMBL:EDN78833.1,
RC ECO:0000312|Proteomes:UP000004410};
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 {ECO:0000312|EMBL:EDN78833.1,
RC ECO:0000312|Proteomes:UP000004410};
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, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBSTRATE
RP SPECIFICITY.
RC STRAIN=ATCC 29149 / VPI C7-9;
RX PubMed=26192599; DOI=10.1038/nchembio.1864;
RA Devlin A.S., Fischbach M.A.;
RT "A biosynthetic pathway for a prominent class of microbiota-derived bile
RT acids.";
RL Nat. Chem. Biol. 11:685-690(2015).
CC -!- FUNCTION: Involved in the modification of secondary bile acids into
CC iso-bile acids (3beta-bile acids) via epimerization of the 3-OH group
CC through a 3-oxo-intermediate. Catalyzes the reduction of 12-alpha-
CC hydroxy-3-oxo-5-beta-cholan-24-oate (3-oxo-DCA) and 3-oxo-5-beta-
CC cholan-24-oate (3-oxo-LCA) to yield isodeoxycholate (isoDCA) and
CC isolithocholate (isoLCA), respectively. Is also able to catalyze the
CC reduction of 3-dehydrocholate (3-oxo-CA or 7alpha,12alpha-dihydroxy-3-
CC oxo-5beta-cholan-24-oate) and 7-alpha-hydroxy-3-oxo-5-beta-cholan-24-
CC oate (3-oxo-CDCA), into isocholate (isoCA) and isochenodeoxycholate
CC (isoCDCA), respectively. Accepts both NADPH and NADH as cosubstrates.
CC The conversion of the abundant bile acid deoxycholate (DCA) into isoDCA
CC by the gut bacterium R.gnavus favors the growth of the keystone
CC commensal genus Bacteroides, since isoDCA is less cytotoxic than its
CC parent compound, DCA; iso-bile acids have thus a potential role in
CC modulating gut community composition. {ECO:0000269|PubMed:26192599}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxo-5beta-cholan-24-oate + H(+) + NADPH = isolithocholate +
CC NADP(+); Xref=Rhea:RHEA:47520, ChEBI:CHEBI:11867, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:87728;
CC EC=1.1.1.393; Evidence={ECO:0000269|PubMed:26192599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47521;
CC Evidence={ECO:0000305|PubMed:26192599};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12alpha-hydroxy-3-oxo-5beta-cholan-24-oate + H(+) + NADPH =
CC isodeoxycholate + NADP(+); Xref=Rhea:RHEA:47488, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:87733,
CC ChEBI:CHEBI:87734; Evidence={ECO:0000269|PubMed:26192599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47489;
CC Evidence={ECO:0000305|PubMed:26192599};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12alpha-hydroxy-3-oxo-5beta-cholan-24-oate + H(+) + NADH =
CC isodeoxycholate + NAD(+); Xref=Rhea:RHEA:47492, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:87733,
CC ChEBI:CHEBI:87734; Evidence={ECO:0000269|PubMed:26192599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47493;
CC Evidence={ECO:0000305|PubMed:26192599};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7alpha,12alpha-dihydroxy-3-oxo-5beta-cholan-24-oate + H(+) +
CC NADPH = isocholate + NADP(+); Xref=Rhea:RHEA:47528,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:87735, ChEBI:CHEBI:87736;
CC Evidence={ECO:0000269|PubMed:26192599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47529;
CC Evidence={ECO:0000305|PubMed:26192599};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7alpha-hydroxy-3-oxo-5beta-cholan-24-oate + H(+) + NADPH =
CC isochenodeoxycholate + NADP(+); Xref=Rhea:RHEA:47536,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:87730, ChEBI:CHEBI:87731;
CC Evidence={ECO:0000269|PubMed:26192599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47537;
CC Evidence={ECO:0000305|PubMed:26192599};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=56 uM for 12alpha-hydroxy-3-oxo-5beta-cholan-24-oate
CC {ECO:0000269|PubMed:26192599};
CC Note=kcat is 9430 min(-1) with 12alpha-hydroxy-3-oxo-5beta-cholan-24-
CC oate as substrate. {ECO:0000269|PubMed:26192599};
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AAYG02000006; EDN78833.1; -; Genomic_DNA.
DR AlphaFoldDB; A7AZH2; -.
DR SMR; A7AZH2; -.
DR STRING; 411470.RUMGNA_00694; -.
DR SwissLipids; SLP:000001344; -.
DR PRIDE; A7AZH2; -.
DR EnsemblBacteria; EDN78833; EDN78833; RUMGNA_00694.
DR KEGG; ag:EDN78833; -.
DR eggNOG; COG1028; Bacteria.
DR BioCyc; MetaCyc:MON-19698; -.
DR BRENDA; 1.1.1.393; 5479.
DR Proteomes; UP000004410; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0008202; P:steroid metabolic process; IEA:UniProtKB-KW.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW Lipid metabolism; NADP; Oxidoreductase; Steroid metabolism.
FT CHAIN 1..276
FT /note="3beta-hydroxysteroid dehydrogenase"
FT /id="PRO_0000443429"
FT ACT_SITE 162
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 70..71
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9ZNN8"
FT BINDING 97
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9ZNN8"
FT BINDING 162
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9ZNN8"
FT BINDING 166
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9ZNN8"
SQ SEQUENCE 276 AA; 29047 MW; 8D2745D901EBCB3D CRC64;
MNFGGFIMGR FDEKIMLVTG ATSGIGRAVA IRAAKEGATV VAVGRNEERG AAVVAAMEEA
GGKGEFMKCD VSNKDAVKAL FAEIQEKYGK LDVAVNNAGI VGASKTVEEL EDDDWFQVID
ANLNSCFFCC REEVKLMQPS GGAIVNVSSV AGMRGFPSAA AYVASKHAVS GLTKAVAVDY
ATKGITCNAI CPAGTDTPLT ERSSADIKTR MAEIAAQGKD PMEWLKNSML SGKTETLQKK
NATPEEQAAT ILYFASDEAR HITGSIVASD GGFTTY
