HDHA_PAESO
ID HDHA_PAESO Reviewed; 267 AA.
AC P50200;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=7alpha-hydroxysteroid dehydrogenase {ECO:0000303|PubMed:8050999};
DE Short=7alpha-HSDH {ECO:0000303|PubMed:8050999};
DE EC=1.1.1.- {ECO:0000269|PubMed:8050999, ECO:0000305|PubMed:11947357};
DE AltName: Full=NADP-dependent 7alpha-hydroxysteroid dehydrogenase {ECO:0000305|PubMed:8050999};
OS Paeniclostridium sordellii (Clostridium sordellii).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Peptostreptococcaceae;
OC Paeniclostridium.
OX NCBI_TaxID=1505;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-18, FUNCTION,
RP CATALYTIC ACTIVITY, INDUCTION, AND SUBUNIT.
RC STRAIN=ATCC 9714 / DSM 2141 / JCM 3814 / LMG 15708 / NCIMB 10717;
RX PubMed=8050999; DOI=10.1128/jb.176.16.4865-4874.1994;
RA Coleman J.P., Hudson L.L., Adams M.J.;
RT "Characterization and regulation of the NADP-linked 7 alpha-hydroxysteroid
RT dehydrogenase gene from Clostridium sordellii.";
RL J. Bacteriol. 176:4865-4874(1994).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 9714 / DSM 2141 / JCM 3814 / LMG 15708 / NCIMB 10717;
RX PubMed=11947357; DOI=10.1016/0014-5793(70)80020-5;
RA Hayakawa S., Hattori T.;
RT "7alpha-dehydroxylation of cholic acid by Clostridium bifermentans strain
RT ATCC 9714 and Clostridium sordellii strain NCIB 6929.";
RL FEBS Lett. 6:131-133(1970).
CC -!- FUNCTION: 7alpha-hydroxysteroid dehydrogenase that catalyzes the
CC NADP(+)-dependent oxidation of the 7alpha-hydroxy group of 7alpha-
CC hydroxysteroids, such as the major human bile acids cholate and
CC chenodeoxycholate, to the corresponding 7-oxosteroids (PubMed:8050999,
CC PubMed:11947357). Is thus liley involved in the metabolism of primary
CC bile acids (PubMed:8050999). {ECO:0000269|PubMed:11947357,
CC ECO:0000269|PubMed:8050999}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholate + NADP(+) = 3alpha,12alpha-dihydroxy-7-oxo-5beta-
CC cholanate + H(+) + NADPH; Xref=Rhea:RHEA:48508, ChEBI:CHEBI:11893,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29747, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; Evidence={ECO:0000305|PubMed:11947357};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48509;
CC Evidence={ECO:0000305|PubMed:11947357};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chenodeoxycholate + NADP(+) = 7-oxolithocholate + H(+) +
CC NADPH; Xref=Rhea:RHEA:53820, ChEBI:CHEBI:15378, ChEBI:CHEBI:36234,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:78605;
CC Evidence={ECO:0000269|PubMed:8050999};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53821;
CC Evidence={ECO:0000269|PubMed:8050999};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:8050999}.
CC -!- INDUCTION: Up-regulated by bile acids, such as cholate and
CC chenodeoxycholate. Maximally expressed during the early stationary
CC phase of growth. {ECO:0000269|PubMed:8050999}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; L12058; AAA53556.1; -; Genomic_DNA.
DR PIR; B55850; B55850.
DR AlphaFoldDB; P50200; -.
DR SMR; P50200; -.
DR STRING; 1292035.H476_2317; -.
DR SwissLipids; SLP:000001735; -.
DR eggNOG; COG1028; Bacteria.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0030573; P:bile acid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0016042; P:lipid catabolic 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 Bile acid catabolism; Direct protein sequencing; Lipid degradation;
KW Lipid metabolism; NADP; Oxidoreductase; Steroid metabolism.
FT CHAIN 1..267
FT /note="7alpha-hydroxysteroid dehydrogenase"
FT /id="PRO_0000054707"
FT ACT_SITE 158
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P0AET8"
FT BINDING 13..18
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G9FRD7"
FT BINDING 38
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G9FRD7"
FT BINDING 63..64
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G9FRD7"
FT BINDING 90
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G9FRD7"
FT BINDING 145
FT /ligand="cholate"
FT /ligand_id="ChEBI:CHEBI:29747"
FT /evidence="ECO:0000250|UniProtKB:G9FRD7, ECO:0000305"
FT BINDING 158
FT /ligand="cholate"
FT /ligand_id="ChEBI:CHEBI:29747"
FT /evidence="ECO:0000250|UniProtKB:G9FRD7, ECO:0000305"
FT BINDING 158
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G9FRD7"
FT BINDING 162
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G9FRD7"
FT BINDING 191..195
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G9FRD7"
FT SITE 145
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P0AET8"
FT SITE 162
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250|UniProtKB:P0AET8"
SQ SEQUENCE 267 AA; 29177 MW; 8560207B9EDCEC0E CRC64;
MNKLENKVAL VTSATRGIGL ASAIKLAQNG AIVYMGVRRL EATQEICDKY KEEGLILKPV
FFDAYNIDIY KEMIDTIIKN EGKIDILVNN FGTGRPEKDL DLVNGDEDTF FELFNYNVGS
VYRLSKLIIP HMIENKGGSI VNISSVGGSI PDISRIGYGV SKSGVNNITK QIAIQYAKYG
IRCNAVLPGL IATDAAMNSM PDEFRKSFLS HVPLNRIGNP EDIANSVLFF VPSEDSSYIT
GSILEVSGGY NLGTPQYAEF VGSKVVE
