BAIA2_CLOSV
ID BAIA2_CLOSV Reviewed; 249 AA.
AC P19337;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=3alpha-hydroxy bile acid-CoA-ester 3-dehydrogenase 2 {ECO:0000305|PubMed:23836456};
DE EC=1.1.1.395 {ECO:0000269|PubMed:23836456};
DE AltName: Full=3alpha-hydroxysteroid dehydrogenase 2 {ECO:0000303|PubMed:16299351, ECO:0000303|PubMed:23836456};
DE Short=3alpha-HSDH 2 {ECO:0000303|PubMed:16299351};
DE AltName: Full=Bile acid-inducible protein BaiA2 {ECO:0000303|PubMed:16299351};
GN Name=baiA2;
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].
RX PubMed=2254270; DOI=10.1128/jb.172.12.7011-7019.1990;
RA Mallonee D.H., White W.B., Hylemon P.B.;
RT "Cloning and sequencing of a bile acid-inducible operon from Eubacterium
RT sp. strain VPI 12708.";
RL J. Bacteriol. 172:7011-7019(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3170477; DOI=10.1128/jb.170.10.4555-4561.1988;
RA White W.B., Franklund C.V., Coleman J.P., Hylemon P.B.;
RT "Evidence for a multigene family involved in bile acid 7-dehydroxylation in
RT Eubacterium sp. strain VPI 12708.";
RL J. Bacteriol. 170:4555-4561(1988).
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 X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH NAD,
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, REACTION MECHANISM, ACTIVE SITE, AND MUTAGENESIS OF
RP GLU-42.
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=32 uM for choloyl-CoA (at pH 8.7 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:23836456};
CC KM=23 uM for chenodeoxycholoyl-CoA (at pH 8.7 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:23836456};
CC KM=18 uM for lithocholoyl-CoA (at pH 8.7 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:23836456};
CC KM=17 uM for deoxycholoyl-CoA (at pH 8.7 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:23836456};
CC KM=1.8 uM for 3-oxocholoyl-CoA (at pH 8.7 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:23836456};
CC KM=1.1 uM for 3-oxochenodeoxycholoyl-CoA (at pH 8.7 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:23836456};
CC KM=1.3 uM for 3-oxolithocholoyl-CoA (at pH 8.7 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:23836456};
CC KM=1.5 uM for 3-oxodeoxycholoyl-CoA (at pH 8.7 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:23836456};
CC KM=6.7 uM for NAD(+) (at pH 8.7 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:23836456};
CC KM=84 uM for NADP(+) (at pH 8.7 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:23836456};
CC Note=kcat is 10 min(-1) with choloyl-CoA as substrate. kcat is 12
CC min(-1) with chenodeoxycholoyl-CoA as substrate. kcat is 11 min(-1)
CC with lithocholoyl-CoA as substrate. kcat is 9.5 min(-1) with
CC deoxycholoyl-CoA as substrate. kcat is 8.3 min(-1) with 3-oxocholoyl-
CC CoA as substrate. kcat is 10 min(-1) with 3-oxochenodeoxycholoyl-CoA
CC as substrate. kcat is 7.3 min(-1) with 3-oxolithocholoyl-CoA as
CC substrate. kcat is 9.1 min(-1) with 3-oxodeoxycholoyl-CoA as
CC substrate (at pH 8.7 and 37 degrees Celsius).
CC {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}.
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DR EMBL; M22623; AAB61150.1; -; Genomic_DNA.
DR EMBL; U57489; AAC45414.1; -; Genomic_DNA.
DR PIR; A31841; A31841.
DR PDB; 4IS2; X-ray; 1.90 A; A=1-249.
DR PDB; 4IS3; X-ray; 2.00 A; A/B/C/D=1-249.
DR PDBsum; 4IS2; -.
DR PDBsum; 4IS3; -.
DR AlphaFoldDB; P19337; -.
DR SMR; P19337; -.
DR SwissLipids; SLP:000001731; -.
DR BioCyc; MetaCyc:BAIA2EUBSP-MON; -.
DR BRENDA; 1.1.1.395; 1513.
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 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 3D-structure; Lipid metabolism; NAD; Oxidoreductase; Steroid metabolism.
FT CHAIN 1..249
FT /note="3alpha-hydroxy bile acid-CoA-ester 3-dehydrogenase
FT 2"
FT /id="PRO_0000054525"
FT ACT_SITE 157
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001,
FT ECO:0000305|PubMed:23836456"
FT ACT_SITE 161
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:23836456"
FT BINDING 15..18
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23836456,
FT ECO:0007744|PDB:4IS3"
FT BINDING 38
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23836456,
FT ECO:0007744|PDB:4IS3"
FT BINDING 42
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23836456,
FT ECO:0007744|PDB:4IS3"
FT BINDING 92
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23836456,
FT ECO:0007744|PDB:4IS3"
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:0000269|PubMed:23836456,
FT ECO:0007744|PDB:4IS3"
FT BINDING 190..192
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23836456,
FT ECO:0007744|PDB:4IS3"
FT MUTAGEN 42
FT /note="E->A: Improves utilization of NADP(+) as cosubstrate
FT by 10-fold compared to wild-type. Displays 6-fold increase
FT in affinity for NADP(+)."
FT /evidence="ECO:0000269|PubMed:23836456"
FT TURN 3..6
FT /evidence="ECO:0007829|PDB:4IS2"
FT STRAND 8..11
FT /evidence="ECO:0007829|PDB:4IS2"
FT TURN 12..15
FT /evidence="ECO:0007829|PDB:4IS2"
FT HELIX 17..28
FT /evidence="ECO:0007829|PDB:4IS2"
FT STRAND 32..36
FT /evidence="ECO:0007829|PDB:4IS2"
FT HELIX 40..53
FT /evidence="ECO:0007829|PDB:4IS2"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:4IS2"
FT HELIX 69..83
FT /evidence="ECO:0007829|PDB:4IS2"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:4IS2"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:4IS2"
FT HELIX 106..116
FT /evidence="ECO:0007829|PDB:4IS2"
FT HELIX 118..131
FT /evidence="ECO:0007829|PDB:4IS2"
FT TURN 132..135
FT /evidence="ECO:0007829|PDB:4IS2"
FT STRAND 137..142
FT /evidence="ECO:0007829|PDB:4IS2"
FT HELIX 146..149
FT /evidence="ECO:0007829|PDB:4IS3"
FT HELIX 160..174
FT /evidence="ECO:0007829|PDB:4IS2"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:4IS2"
FT STRAND 180..187
FT /evidence="ECO:0007829|PDB:4IS2"
FT HELIX 193..196
FT /evidence="ECO:0007829|PDB:4IS3"
FT HELIX 200..209
FT /evidence="ECO:0007829|PDB:4IS3"
FT HELIX 218..229
FT /evidence="ECO:0007829|PDB:4IS2"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:4IS2"
FT STRAND 238..243
FT /evidence="ECO:0007829|PDB:4IS2"
SQ SEQUENCE 249 AA; 26538 MW; 9A39B78BB63DC5AF CRC64;
MNLVQDKVTI ITGGTRGIGF AAAKIFIDNG AKVSIFGETQ EEVDTALAQL KELYPEEEVL
GFAPDLTSRD AVMAAVGQVA QKYGRLDVMI NNAGITSNNV FSRVSEEEFK HIMDINVTGV
FNGAWCAYQC MKDAKKGVII NTASVTGIFG SLSGVGYPAS KASVIGLTHG LGREIIRKNI
RVVGVAPGVV NTDMTNGNPP EIMEGYLKAL PMKRMLEPEE IANVYLFLAS DLASGITATT
VSVDGAYRP
