3AHDP_RUMGV
ID 3AHDP_RUMGV Reviewed; 250 AA.
AC A7B3K3;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=3alpha-hydroxysteroid dehydrogenase {ECO:0000303|PubMed:26192599};
DE Short=3alpha-HSDH {ECO:0000303|PubMed:26192599};
DE EC=1.1.1.- {ECO:0000269|PubMed:26192599};
DE AltName: Full=3alpha-hydroxycholanate dehydrogenase (NADP(+));
DE EC=1.1.1.392 {ECO:0000269|PubMed:26192599};
DE AltName: Full=NADP-dependent bile acid 3alpha-dehydrogenase {ECO:0000305};
GN Name=baiA {ECO:0000312|EMBL:EDN77529.1};
GN ORFNames=RUMGNA_02133 {ECO:0000312|EMBL:EDN77529.1};
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:EDN77529.1,
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:EDN77529.1,
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 oxidation of deoxycholate
CC (DCA) and lithocholate (LCA) to yield 12-alpha-hydroxy-3-oxo-5-beta-
CC cholan-24-oate (3-oxo-DCA) and 3-oxo-5-beta-cholan-24-oate (3-oxo-LCA),
CC respectively. Is also able to catalyze the oxidation of cholate (CA)
CC and chenodeoxycholate (CDCA) into 3-dehydrocholate (3-oxo-CA) and 7-
CC alpha-hydroxy-3-oxo-5-beta-cholan-24-oate (3-oxo-CDCA), respectively.
CC Can also catalyze the reverse reactions in vitro. Accepts both NADPH
CC and NADH as cosubstrates. The conversion of the abundant bile acid DCA
CC into isoDCA by the gut bacterium R.gnavus favors the growth of the
CC keystone commensal genus Bacteroides, since isoDCA is less cytotoxic
CC than its parent compound, DCA; iso-bile acids have thus a potential
CC role in modulating gut community composition.
CC {ECO:0000269|PubMed:26192599}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lithocholate + NADP(+) = 3-oxo-5beta-cholan-24-oate + H(+) +
CC NADPH; Xref=Rhea:RHEA:47496, ChEBI:CHEBI:11867, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29744, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.392; Evidence={ECO:0000269|PubMed:26192599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47497;
CC Evidence={ECO:0000305|PubMed:26192599};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=deoxycholate + NADP(+) = 12alpha-hydroxy-3-oxo-5beta-cholan-
CC 24-oate + H(+) + NADPH; Xref=Rhea:RHEA:47480, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:23614, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:87734; Evidence={ECO:0000269|PubMed:26192599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47481;
CC Evidence={ECO:0000305|PubMed:26192599};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=deoxycholate + NAD(+) = 12alpha-hydroxy-3-oxo-5beta-cholan-24-
CC oate + H(+) + NADH; Xref=Rhea:RHEA:47484, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:23614, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:87734; Evidence={ECO:0000269|PubMed:26192599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47485;
CC Evidence={ECO:0000305|PubMed:26192599};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholate + NADP(+) = 7alpha,12alpha-dihydroxy-3-oxo-5beta-
CC cholan-24-oate + H(+) + NADPH; Xref=Rhea:RHEA:47500,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29747, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:87736;
CC Evidence={ECO:0000269|PubMed:26192599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47501;
CC Evidence={ECO:0000305|PubMed:26192599};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chenodeoxycholate + NADP(+) = 7alpha-hydroxy-3-oxo-5beta-
CC cholan-24-oate + H(+) + NADPH; Xref=Rhea:RHEA:47504,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:36234, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:87731;
CC Evidence={ECO:0000269|PubMed:26192599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47505;
CC Evidence={ECO:0000305|PubMed:26192599};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=369 uM for deoxycholate {ECO:0000269|PubMed:26192599};
CC Note=kcat is 99.3 min(-1) with deoxycholate as substrate.
CC {ECO:0000269|PubMed:26192599};
CC pH dependence:
CC Transformation of DCA is more efficient at pH 10 than pH 7.
CC {ECO:0000269|PubMed:26192599};
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AAYG02000016; EDN77529.1; -; Genomic_DNA.
DR AlphaFoldDB; A7B3K3; -.
DR STRING; 411470.RUMGNA_02133; -.
DR SwissLipids; SLP:000001340; -.
DR PRIDE; A7B3K3; -.
DR EnsemblBacteria; EDN77529; EDN77529; RUMGNA_02133.
DR KEGG; ag:EDN77529; -.
DR eggNOG; COG1028; Bacteria.
DR BioCyc; MetaCyc:MON-19696; -.
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 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..250
FT /note="3alpha-hydroxysteroid dehydrogenase"
FT /id="PRO_0000443426"
FT ACT_SITE 158
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 93
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9ZNN8"
FT BINDING 158
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"
SQ SEQUENCE 250 AA; 26568 MW; CDB5637133C4C1EA CRC64;
MFMMLKNKVA IVTGGTRGIG FAVVKKFIEN GAAVSLWGSR QETVDQALEQ LKELYPDAKI
SGKYPSLKDT AQVTAMINQV KEEFGAVDIL VNNAGISQST SFYNYQPEEF QKIVDLNVTA
VFNCSQAAAK IMKEQGGGVI LNTSSMVSIY GQPSGCGYPA SKFAVNGLTK SLARELGCDN
IRVNAVAPGI TRTDMVAALP EAVIKPLIAT IPLGRVGEPE DIANAFLFLA SDMASYVTGE
ILSVDGAARS
