3BHD2_EGGLE
ID 3BHD2_EGGLE Reviewed; 260 AA.
AC C8WGQ3;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 1.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=3beta-hydroxysteroid dehydrogenase 2 {ECO:0000303|PubMed:26192599};
DE Short=3beta-HSDH 2 {ECO:0000303|PubMed:26192599};
DE EC=1.1.1.- {ECO:0000269|PubMed:26192599};
DE AltName: Full=3beta-hydroxycholanate 3-dehydrogenase (NAD(+)) 2;
DE EC=1.1.1.391 {ECO:0000269|PubMed:26192599};
DE AltName: Full=NAD-dependent bile acid 3beta-dehydrogenase {ECO:0000305};
GN OrderedLocusNames=Elen_1325 {ECO:0000312|EMBL:ACV55294.1};
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 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 NADH and NADPH as cosubstrates.
CC The conversion of the abundant bile acid deoxycholate (DCA) into isoDCA
CC 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=3-oxo-5beta-cholan-24-oate + H(+) + NADH = isolithocholate +
CC NAD(+); Xref=Rhea:RHEA:47508, ChEBI:CHEBI:11867, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:87728;
CC EC=1.1.1.391; Evidence={ECO:0000269|PubMed:26192599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47509;
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=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=7alpha,12alpha-dihydroxy-3-oxo-5beta-cholan-24-oate + H(+) +
CC NADH = isocholate + NAD(+); Xref=Rhea:RHEA:47512, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:87735,
CC ChEBI:CHEBI:87736; Evidence={ECO:0000269|PubMed:26192599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47513;
CC Evidence={ECO:0000305|PubMed:26192599};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7alpha-hydroxy-3-oxo-5beta-cholan-24-oate + H(+) + NADH =
CC isochenodeoxycholate + NAD(+); Xref=Rhea:RHEA:47516,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:87730, ChEBI:CHEBI:87731;
CC Evidence={ECO:0000269|PubMed:26192599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47517;
CC Evidence={ECO:0000305|PubMed:26192599};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2630 uM for 12alpha-hydroxy-3-oxo-5beta-cholan-24-oate
CC {ECO:0000269|PubMed:26192599};
CC Note=kcat is 1750 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}.
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; CP001726; ACV55294.1; -; Genomic_DNA.
DR RefSeq; WP_015760525.1; NC_013204.1.
DR AlphaFoldDB; C8WGQ3; -.
DR SMR; C8WGQ3; -.
DR STRING; 479437.Elen_1325; -.
DR SwissLipids; SLP:000001343; -.
DR EnsemblBacteria; ACV55294; ACV55294; Elen_1325.
DR KEGG; ele:Elen_1325; -.
DR eggNOG; COG1028; Bacteria.
DR HOGENOM; CLU_010194_1_0_11; -.
DR OrthoDB; 1356861at2; -.
DR BioCyc; ELEN479437:G1GFY-1333-MON; -.
DR BRENDA; 1.1.1.391; 2185.
DR Proteomes; UP000001377; Chromosome.
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; NAD; Oxidoreductase; Reference proteome;
KW Steroid metabolism.
FT CHAIN 1..260
FT /note="3beta-hydroxysteroid dehydrogenase 2"
FT /id="PRO_0000443428"
FT ACT_SITE 163
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 43
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9ZNN8"
FT BINDING 69..70
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9ZNN8"
FT BINDING 96
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9ZNN8"
FT BINDING 163
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9ZNN8"
FT BINDING 167
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9ZNN8"
SQ SEQUENCE 260 AA; 27311 MW; 6223630A142E967E CRC64;
MSEARHNPVL AGQTAVITGG ASGIGKSIVQ RFLEAGASCL AADLNEEALA ALKQELAEYG
DKLDVVKVDV SNRDDVEGMV DRAVQTFGQM DIIVNNAGIM DNLLPIAEMD DDVWERLMKV
NLNSVMYGTR KAVRYFMERG EGGVIINTAS LSGLCAGRGG CAYTASKFAV VGLTKNVAFM
YADTGIRCNA ICPGNTQTNI GVGMRQPSER GMAKATTGYA GATRSGTPEE ISAAAAFLAS
DQAGFINGET LTIDGGWSAY
