BAIA1_CLOSV
ID BAIA1_CLOSV Reviewed; 249 AA.
AC P07914;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 3.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=3alpha-hydroxy bile acid-CoA-ester 3-dehydrogenase 1/3 {ECO:0000305|PubMed:23836456};
DE EC=1.1.1.395 {ECO:0000269|PubMed:23836456};
DE AltName: Full=3alpha-hydroxysteroid dehydrogenase 1/3 {ECO:0000303|PubMed:16299351, ECO:0000303|PubMed:23836456};
DE Short=3alpha-HSDH 1/3 {ECO:0000303|PubMed:16299351};
DE AltName: Full=Bile acid-inducible protein BaiA1 {ECO:0000303|PubMed:16299351};
DE AltName: Full=Bile acid-inducible protein BaiA3 {ECO:0000303|PubMed:16299351};
GN Name=baiA1;
GN and
GN Name=baiA3;
OS Clostridium scindens (strain JCM 10418 / VPI 12708).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Lachnospiraceae.
OX NCBI_TaxID=29347;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (BAIA3).
RX PubMed=2376563; DOI=10.1128/jb.172.8.4420-4426.1990;
RA Gopal-Srivastava R., Mallonee D.H., White W.B., Hylemon P.B.;
RT "Multiple copies of a bile acid-inducible gene in Eubacterium sp. strain
RT VPI 12708.";
RL J. Bacteriol. 172:4420-4426(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (BAIA1).
RX PubMed=2834320; DOI=10.1128/jb.170.5.2070-2077.1988;
RA Coleman J.P., White W.B., Lijewski M., Hylemon P.B.;
RT "Nucleotide sequence and regulation of a gene involved in bile acid 7-
RT dehydroxylation by Eubacterium sp. strain VPI 12708.";
RL J. Bacteriol. 170:2070-2077(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-55 (BAIA1), AND PROTEIN SEQUENCE OF
RP 1-33.
RX PubMed=3549693; DOI=10.1128/jb.169.4.1516-1521.1987;
RA Coleman J.P., White W.B., Hylemon P.B.;
RT "Molecular cloning of bile acid 7-dehydroxylase from Eubacterium sp. strain
RT VPI 12708.";
RL J. Bacteriol. 169:1516-1521(1987).
RN [4]
RP REVIEW, FUNCTION, INDUCTION, AND PATHWAY.
RX PubMed=16299351; DOI=10.1194/jlr.r500013-jlr200;
RA Ridlon J.M., Kang D.J., Hylemon P.B.;
RT "Bile salt biotransformations by human intestinal bacteria.";
RL J. Lipid Res. 47:241-259(2006).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, REACTION MECHANISM, AND PATHWAY.
RC STRAIN=JCM 10418 / VPI 12708;
RX PubMed=23836456; DOI=10.1002/prot.24353;
RA Bhowmik S., Jones D.H., Chiu H.P., Park I.H., Chiu H.J., Axelrod H.L.,
RA Farr C.L., Tien H.J., Agarwalla S., Lesley S.A.;
RT "Structural and functional characterization of BaiA, an enzyme involved in
RT secondary bile acid synthesis in human gut microbe.";
RL Proteins 82:216-229(2014).
CC -!- FUNCTION: Involved in the multi-step bile acid 7alpha-dehydroxylation
CC pathway that transforms primary bile acids to secondary bile acids in
CC the human gut (PubMed:23836456, PubMed:16299351). Catalyzes the
CC oxidation of C3-hydroxyl group of CoA conjugated bile acids generating
CC a C3-oxo bile acid intermediate. Can use choloyl-CoA,
CC chenodeoxycholoyl-CoA, deoxycholoyl-CoA, and lithocholoyl-CoA as
CC substrates with similar efficiency. Highly prefers NAD over NADP as
CC cosubstrate. Also catalyzes the reverse reactions; in vitro, the
CC preferred direction of reaction depends on the pH. Has very little
CC activity with unconjugated (non-CoA) bile acid substrates
CC (PubMed:23836456). {ECO:0000269|PubMed:23836456,
CC ECO:0000303|PubMed:16299351}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3alpha-hydroxy bile acid CoA + NAD(+) = a 3-oxo bile acid
CC CoA + H(+) + NADH; Xref=Rhea:RHEA:55380, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:138842,
CC ChEBI:CHEBI:138843; EC=1.1.1.395;
CC Evidence={ECO:0000269|PubMed:23836456};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=choloyl-CoA + NAD(+) = 7alpha,12alpha-dihydroxy-3-oxochol-24-
CC oyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:52588, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57373, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:136700; EC=1.1.1.395;
CC Evidence={ECO:0000269|PubMed:23836456};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chenodeoxycholoyl-CoA + NAD(+) = 7alpha-hydroxy-3-oxochol-24-
CC oyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:52584, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62989,
CC ChEBI:CHEBI:136698; EC=1.1.1.395;
CC Evidence={ECO:0000269|PubMed:23836456};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=deoxycholoyl-CoA + NAD(+) = 12alpha-hydroxy-3-oxocholan-24-
CC oyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:52592, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58810,
CC ChEBI:CHEBI:136701; EC=1.1.1.395;
CC Evidence={ECO:0000269|PubMed:23836456};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lithocholoyl-CoA + NAD(+) = 3-oxocholan-24-oyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:52596, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:87438, ChEBI:CHEBI:136703;
CC EC=1.1.1.395; Evidence={ECO:0000269|PubMed:23836456};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=106 uM for choloyl-CoA (at pH 8.7 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:23836456};
CC KM=53 uM for chenodeoxycholoyl-CoA (at pH 8.7 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:23836456};
CC KM=22 uM for lithocholoyl-CoA (at pH 8.7 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:23836456};
CC KM=16 uM for deoxycholoyl-CoA (at pH 8.7 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:23836456};
CC KM=9.1 uM for 3-oxocholoyl-CoA (at pH 8.7 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:23836456};
CC KM=3.3 uM for 3-oxochenodeoxycholoyl-CoA (at pH 8.7 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:23836456};
CC KM=8.3 uM for 3-oxolithocholoyl-CoA (at pH 8.7 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:23836456};
CC KM=5.6 uM for 3-oxodeoxycholoyl-CoA (at pH 8.7 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:23836456};
CC KM=17 uM for NAD(+) (at pH 8.7 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:23836456};
CC KM=883 uM for NADP(+) (at pH 8.7 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:23836456};
CC Note=kcat is 74 min(-1) with choloyl-CoA as substrate. kcat is 49
CC min(-1) with chenodeoxycholoyl-CoA as substrate. kcat is 44 min(-1)
CC with lithocholoyl-CoA as substrate. kcat is 52 min(-1) with
CC deoxycholoyl-CoA as substrate. kcat is 33 min(-1) with 3-oxocholoyl-
CC CoA as substrate. kcat is 24 min(-1) with 3-oxochenodeoxycholoyl-CoA
CC as substrate. kcat is 42 min(-1) with 3-oxolithocholoyl-CoA as
CC substrate. kcat is 44 min(-1) with 3-oxodeoxycholoyl-CoA as substrate
CC (at pH 8.7 and 37 degrees Celsius). {ECO:0000269|PubMed:23836456};
CC pH dependence:
CC The direction of reaction is pH dependent in vitro. At pH 7.3,
CC clearly the reduction reaction is preferred with an order of
CC magnitude higher velocity than the oxidation reaction. At pH 8.7, the
CC velocities of the oxidation and reduction reaction are comparable. At
CC pH 9.9 the velocity of the reduction reaction is about 60% of
CC oxidation reaction. {ECO:0000269|PubMed:23836456};
CC -!- PATHWAY: Lipid metabolism; bile acid biosynthesis.
CC {ECO:0000303|PubMed:16299351, ECO:0000305|PubMed:23836456}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:23836456}.
CC -!- INDUCTION: Induced by the C24 primary bile acids cholic acid (CA) and
CC chenodeoxycholic acid (CDCA). {ECO:0000303|PubMed:16299351}.
CC -!- MISCELLANEOUS: There are three genes for BaiA proteins: baiA1 is
CC identical to baiA3 and encodes a polypeptide sharing 92% identity with
CC baiA2 gene product. {ECO:0000305}.
CC -!- MISCELLANEOUS: Reaction mechanism seems to proceed via a nicotinamide-
CC OH(-) adduct, which is proposed to be involved in proton relay instead
CC of hydride transfer. {ECO:0000305|PubMed:23836456}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- CAUTION: Was originally named bile acid 7-dehydroxylase
CC (PubMed:3549693). In fact, the 7-dehydroxylation process is catalyzed
CC by multiple enzymes. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M34658; AAB61155.1; -; Genomic_DNA.
DR EMBL; M19654; AAB61154.1; -; Genomic_DNA.
DR EMBL; M15813; AAB61153.1; -; Genomic_DNA.
DR PIR; B37762; B37762.
DR RefSeq; WP_025644109.1; NZ_JAAISN010000001.1.
DR AlphaFoldDB; P07914; -.
DR SwissLipids; SLP:000001732; -.
DR BioCyc; MetaCyc:BAIA1EUBSP-MON; -.
DR UniPathway; UPA00221; -.
DR GO; GO:0033792; F:3alpha-hydroxy bile acid-CoA-ester 3-dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0032052; F:bile acid binding; IDA:UniProtKB.
DR GO; GO:0070403; F:NAD+ binding; IDA: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:0006699; P:bile acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0008206; P:bile acid metabolic process; IDA:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:1903412; P:response to bile acid; TAS:UniProtKB.
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 Direct protein sequencing; Lipid metabolism; NAD; Oxidoreductase;
KW Steroid metabolism.
FT CHAIN 1..249
FT /note="3alpha-hydroxy bile acid-CoA-ester 3-dehydrogenase
FT 1/3"
FT /id="PRO_0000054524"
FT ACT_SITE 157
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P19337,
FT ECO:0000255|PROSITE-ProRule:PRU10001"
FT ACT_SITE 161
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P19337"
FT BINDING 15..18
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P19337"
FT BINDING 38
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P19337"
FT BINDING 42
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P19337"
FT BINDING 92
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P19337"
FT BINDING 144
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 161
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P19337"
FT BINDING 190..192
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P19337"
FT CONFLICT 159..162
FT /note="TSKA -> YQGG (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 249 AA; 26658 MW; 084E380921D72C93 CRC64;
MKLVQDKITI ITGGTRGIGF AAAKLFIENG AKVSIFGETQ EEVDTALAQL KELYPEEEVL
GFAPDLTSRD AVMAAVGTVA QKYGRLDVMI NNAGITMNSV FSRVSEEDFK NIMDINVNGV
FNGAWSAYQC MKDAKQGVII NTASVTGIYG SLSGIGYPTS KAGVIGLTHG LGREIIRKNI
RVVGVAPGVV DTDMTKGLPP EILEDYLKTL PMKRMLKPEE IANVYLFLAS DLASGITATT
ISVDGAYRP
