3AHD_EGGLE
ID 3AHD_EGGLE Reviewed; 259 AA.
AC C8WMP0;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 1.
DT 03-AUG-2022, entry version 64.
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 (NAD(+));
DE EC=1.1.1.52 {ECO:0000269|PubMed:26192599};
DE AltName: Full=NAD-dependent bile acid 3alpha-dehydrogenase {ECO:0000305};
GN OrderedLocusNames=Elen_0690 {ECO:0000312|EMBL:ACV54671.1};
OS Eggerthella lenta (strain ATCC 25559 / DSM 2243 / CCUG 17323 / JCM 9979 /
OS KCTC 3265 / NCTC 11813 / VPI 0255 / 1899 B) (Eubacterium lentum).
OC Bacteria; Actinobacteria; Coriobacteriia; Eggerthellales; Eggerthellaceae;
OC Eggerthella.
OX NCBI_TaxID=479437;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25559 / DSM 2243 / CCUG 17323 / JCM 9979 / KCTC 3265 / NCTC
RC 11813 / VPI 0255 / 1899 B {ECO:0000312|Proteomes:UP000001377};
RX PubMed=21304654; DOI=10.4056/sigs.33592;
RA Saunders E., Pukall R., Abt B., Lapidus A., Glavina Del Rio T.,
RA Copeland A., Tice H., Cheng J.F., Lucas S., Chen F., Nolan M., Bruce D.,
RA Goodwin L., Pitluck S., Ivanova N., Mavromatis K., Ovchinnikova G.,
RA Pati A., Chen A., Palaniappan K., Land M., Hauser L., Chang Y.J.,
RA Jeffries C.D., Chain P., Meincke L., Sims D., Brettin T., Detter J.C.,
RA Goker M., Bristow J., Eisen J.A., Markowitz V., Hugenholtz P.,
RA Kyrpides N.C., Klenk H.P., Han C.;
RT "Complete genome sequence of Eggerthella lenta type strain (IPP VPI
RT 0255).";
RL Stand. Genomic Sci. 1:174-182(2009).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBSTRATE
RP SPECIFICITY.
RC STRAIN=ATCC 25559 / DSM 2243 / CCUG 17323 / JCM 9979 / KCTC 3265 / NCTC
RC 11813 / VPI 0255 / 1899 B;
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. Prefers NADH to NADPH
CC as cosubstrate. The conversion of the abundant bile acid DCA into
CC isoDCA by the gut bacterium E.lenta 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=lithocholate + NAD(+) = 3-oxo-5beta-cholan-24-oate + H(+) +
CC NADH; Xref=Rhea:RHEA:19585, ChEBI:CHEBI:11867, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29744, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.52;
CC Evidence={ECO:0000269|PubMed:26192599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19586;
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 + NAD(+) = 7alpha,12alpha-dihydroxy-3-oxo-5beta-
CC cholan-24-oate + H(+) + NADH; Xref=Rhea:RHEA:47524,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29747, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:87736;
CC Evidence={ECO:0000269|PubMed:26192599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47525;
CC Evidence={ECO:0000305|PubMed:26192599};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chenodeoxycholate + NAD(+) = 7alpha-hydroxy-3-oxo-5beta-
CC cholan-24-oate + H(+) + NADH; Xref=Rhea:RHEA:47532,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:36234, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:87731;
CC Evidence={ECO:0000269|PubMed:26192599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47533;
CC Evidence={ECO:0000305|PubMed:26192599};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1280 uM for deoxycholate {ECO:0000269|PubMed:26192599};
CC Note=kcat is 291 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; CP001726; ACV54671.1; -; Genomic_DNA.
DR RefSeq; WP_009306474.1; NC_013204.1.
DR AlphaFoldDB; C8WMP0; -.
DR SMR; C8WMP0; -.
DR STRING; 479437.Elen_0690; -.
DR SwissLipids; SLP:000001341; -.
DR EnsemblBacteria; ACV54671; ACV54671; Elen_0690.
DR GeneID; 56789104; -.
DR KEGG; ele:Elen_0690; -.
DR eggNOG; COG1028; Bacteria.
DR HOGENOM; CLU_010194_1_0_11; -.
DR OMA; GYANYSS; -.
DR OrthoDB; 1601931at2; -.
DR BioCyc; ELEN479437:G1GFY-698-MON; -.
DR BioCyc; MetaCyc:MON-19697; -.
DR BRENDA; 1.1.1.392; 2185.
DR Proteomes; UP000001377; Chromosome.
DR GO; GO:0047043; F:3-alpha-hydroxycholanate dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0008202; P:steroid metabolic 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 Lipid metabolism; NAD; Oxidoreductase; Reference proteome;
KW Steroid metabolism.
FT CHAIN 1..259
FT /note="3alpha-hydroxysteroid dehydrogenase"
FT /id="PRO_0000443425"
FT ACT_SITE 154
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 32
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9ZNN8"
FT BINDING 154
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9ZNN8"
FT BINDING 158
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9ZNN8"
SQ SEQUENCE 259 AA; 27383 MW; B6FBC4B5AD38D4E0 CRC64;
MGIYVITGAT SGIGAKTAEI LRERGHEVVN IDLNGGDINA NLATKEGRAG AIAELHERFP
EGIDAMICNA GVSGGKVPIS LIISLNYFGA TEMARGVFDL LEKKGGSCVV TSSNSIAQGA
ARMDVAGMLN NHADEDRILE LVKDVDPAIG HVYYASTKYA LARWVRRMSP DWGSRGVRLN
AIAPGNVRTA MTANMLPEQR AAMEAIPVPT HFGEEPLMDP VEIANAMAFI ASPEASGING
VVLFVDGGTD ALLNSEKVY
