3BHD1_EGGLE
ID 3BHD1_EGGLE Reviewed; 261 AA.
AC C8WJW0;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=3beta-hydroxysteroid dehydrogenase 1 {ECO:0000303|PubMed:26192599};
DE Short=3beta-HSDH 1 {ECO:0000303|PubMed:26192599};
DE EC=1.1.1.- {ECO:0000269|PubMed:26192599};
DE AltName: Full=3beta-hydroxycholanate 3-dehydrogenase (NAD(+)) 1;
DE EC=1.1.1.391 {ECO:0000269|PubMed:26192599};
DE AltName: Full=NAD-dependent bile acid 3beta-dehydrogenase {ECO:0000305};
GN OrderedLocusNames=Elen_0198 {ECO:0000312|EMBL:ACV54192.1};
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. Prefers NADH to NADPH as cosubstrate. The
CC conversion of the abundant bile acid deoxycholate (DCA) into isoDCA by
CC the gut bacterium E.lenta favors the growth of the keystone commensal
CC genus Bacteroides, since isoDCA is less cytotoxic than its parent
CC compound, DCA; iso-bile acids have thus a potential role in modulating
CC 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=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=2660 uM for 12alpha-hydroxy-3-oxo-5beta-cholan-24-oate
CC {ECO:0000269|PubMed:26192599};
CC Note=kcat is 584 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}.
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DR EMBL; CP001726; ACV54192.1; -; Genomic_DNA.
DR RefSeq; WP_015759877.1; NC_013204.1.
DR AlphaFoldDB; C8WJW0; -.
DR SMR; C8WJW0; -.
DR STRING; 479437.Elen_0198; -.
DR SwissLipids; SLP:000001342; -.
DR EnsemblBacteria; ACV54192; ACV54192; Elen_0198.
DR GeneID; 56791206; -.
DR KEGG; ele:Elen_0198; -.
DR eggNOG; COG1028; Bacteria.
DR HOGENOM; CLU_010194_1_3_11; -.
DR OMA; TESMIPM; -.
DR OrthoDB; 1356861at2; -.
DR BioCyc; ELEN479437:G1GFY-208-MON; -.
DR BioCyc; MetaCyc:MON-19699; -.
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..261
FT /note="3beta-hydroxysteroid dehydrogenase 1"
FT /id="PRO_0000443427"
FT ACT_SITE 158
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 65..66
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9ZNN8"
FT BINDING 92
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"
FT BINDING 162
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9ZNN8"
SQ SEQUENCE 261 AA; 27644 MW; D11F97FA92AF259F CRC64;
MYDDLKGKTV VVTGSSKGLG AAMARRFGAE GMNVVANYRS DEEGARETVR AIEEAGGAAA
AVQADVSKNE CVDALFDAAM FSFGGVDIWV NNAGIEVASP SDRKSIEEWQ RVIDVNLTGV
FAGCRRAIDH FLDRKMPGVI INLSSVHEII PWPHFADYAA SKAGVGMLTK TLALEYADRG
IRVNAIAPGA MNTPINAEKF ADPEARAATE RLIPMGYVGA PEDVAAAAAW LASDQASYVT
GTTLFVDGGM TLYPGFQFGQ G
