DIDH_COMTE
ID DIDH_COMTE Reviewed; 257 AA.
AC P80702; Q9ZFY9;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 2.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=3-alpha-hydroxysteroid dehydrogenase/carbonyl reductase;
DE Short=3-alpha-HSD;
DE EC=1.1.1.50;
DE AltName: Full=3-alpha-hydroxysteroid dehydrogenase/3-oxosteroid reductase;
DE AltName: Full=HSD28;
DE AltName: Full=Hydroxyprostaglandin dehydrogenase;
GN Name=hsdA;
OS Comamonas testosteroni (Pseudomonas testosteroni).
OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales;
OC Comamonadaceae; Comamonas.
OX NCBI_TaxID=285;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 11996 / DSM 50244 / IAM 12419 / JCM 5832 / NCIMB 8955 / NBRC
RC 14951 / NCTC 10698 / NRRL B-2611;
RX PubMed=9812981; DOI=10.1074/jbc.273.47.30888;
RA Mobus E., Maser E.;
RT "Molecular cloning, overexpression, and characterization of steroid-
RT inducible 3-alpha-hydroxysteroid dehydrogenase/carbonyl reductase from
RT Comamonas testosteroni. A novel member of the short-chain
RT dehydrogenase/reductase superfamily.";
RL J. Biol. Chem. 273:30888-30896(1998).
RN [2]
RP PROTEIN SEQUENCE OF 2-31, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, AND INDUCTION.
RC STRAIN=ATCC 11996 / DSM 50244 / IAM 12419 / JCM 5832 / NCIMB 8955 / NBRC
RC 14951 / NCTC 10698 / NRRL B-2611;
RX PubMed=8944761; DOI=10.1111/j.1432-1033.1996.00744.x;
RA Oppermann U.C.T., Maser E.;
RT "Characterization of a 3 alpha-hydroxysteroid dehydrogenase/carbonyl
RT reductase from the Gram-negative bacterium Comamonas testosteroni.";
RL Eur. J. Biochem. 241:744-749(1996).
RN [3]
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=10833462; DOI=10.1006/bbrc.2000.2813;
RA Maser E., Mobus E., Xiong G.;
RT "Functional expression, purification, and characterization of 3alpha-
RT hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas
RT testosteroni.";
RL Biochem. Biophys. Res. Commun. 272:622-628(2000).
RN [4]
RP INDUCTION.
RC STRAIN=ATCC 11996 / DSM 50244 / IAM 12419 / JCM 5832 / NCIMB 8955 / NBRC
RC 14951 / NCTC 10698 / NRRL B-2611;
RX PubMed=11139589; DOI=10.1074/jbc.m010962200;
RA Xiong G., Maser E.;
RT "Regulation of the steroid-inducible 3-alpha-hydroxysteroid
RT dehydrogenase/carbonyl reductase gene in Comamonas testosteroni.";
RL J. Biol. Chem. 276:9961-9970(2001).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.68 ANGSTROMS) ALONE AND IN COMPLEX WITH NAD, AND
RP SUBUNIT.
RX PubMed=11007791; DOI=10.1074/jbc.m007559200;
RA Grimm C., Maser E., Mobus E., Klebe G., Reuter K., Ficner R.;
RT "The crystal structure of 3alpha -hydroxysteroid dehydrogenase/carbonyl
RT reductase from Comamonas testosteroni shows a novel oligomerization pattern
RT within the short chain dehydrogenase/reductase family.";
RL J. Biol. Chem. 275:41333-41339(2000).
CC -!- FUNCTION: Catalyzes the reversible interconversion of hydroxy and oxo
CC groups at position 3 of the steroid nucleus. Along with the 3 alpha-
CC hydroxysteroid dehydrogenase and 3-oxo-reductase activities towards a
CC variety of cis or trans fused A/B ring steroids, it also reduces
CC several xenobiotic carbonyl compounds, including a metyrapone-based
CC class of insecticides, to the respective alcohol metabolites. No
CC detectable activity on testosterone, progesterone or 3-oxo-desogestrel.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3alpha-hydroxysteroid + NADP(+) = a 3-oxosteroid + H(+) +
CC NADPH; Xref=Rhea:RHEA:34783, ChEBI:CHEBI:15378, ChEBI:CHEBI:36835,
CC ChEBI:CHEBI:47788, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.50;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3alpha-hydroxysteroid + NAD(+) = a 3-oxosteroid + H(+) +
CC NADH; Xref=Rhea:RHEA:34779, ChEBI:CHEBI:15378, ChEBI:CHEBI:36835,
CC ChEBI:CHEBI:47788, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.50;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=35.7 uM for androstandione {ECO:0000269|PubMed:10833462,
CC ECO:0000269|PubMed:8944761};
CC KM=24.4 uM for androsterone {ECO:0000269|PubMed:10833462,
CC ECO:0000269|PubMed:8944761};
CC KM=3.0 uM for fusidic acid {ECO:0000269|PubMed:10833462,
CC ECO:0000269|PubMed:8944761};
CC KM=610 uM for metyrapone {ECO:0000269|PubMed:10833462,
CC ECO:0000269|PubMed:8944761};
CC Vmax=52.3 umol/min/mg enzyme for androstandione
CC {ECO:0000269|PubMed:10833462, ECO:0000269|PubMed:8944761};
CC Vmax=10.3 umol/min/mg enzyme for androsterone
CC {ECO:0000269|PubMed:10833462, ECO:0000269|PubMed:8944761};
CC Vmax=18.1 umol/min/mg enzyme fusidic acid
CC {ECO:0000269|PubMed:10833462, ECO:0000269|PubMed:8944761};
CC Vmax=0.63 umol/min/mg enzyme metyrapone {ECO:0000269|PubMed:10833462,
CC ECO:0000269|PubMed:8944761};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10833462,
CC ECO:0000269|PubMed:11007791}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:8944761}.
CC -!- INDUCTION: By steroids. Derepression of gene transcription occurs by
CC binding of the steroid inducer molecule to a repressor protein.
CC {ECO:0000269|PubMed:11139589, ECO:0000269|PubMed:8944761}.
CC -!- MISCELLANEOUS: This protein is thought to initiate prokaryotic steroid
CC catabolism.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AF092031; AAC79849.1; -; Genomic_DNA.
DR PIR; JC7291; JC7291.
DR RefSeq; WP_003078312.1; NZ_UFXL01000001.1.
DR PDB; 1FJH; X-ray; 1.68 A; A/B=1-257.
DR PDB; 1FK8; X-ray; 1.95 A; A/B=1-257.
DR PDBsum; 1FJH; -.
DR PDBsum; 1FK8; -.
DR AlphaFoldDB; P80702; -.
DR SMR; P80702; -.
DR GeneID; 64000201; -.
DR BioCyc; MetaCyc:MON-16934; -.
DR BRENDA; 1.1.1.357; 1590.
DR BRENDA; 1.1.1.50; 1590.
DR SABIO-RK; P80702; -.
DR EvolutionaryTrace; P80702; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0047042; F:androsterone dehydrogenase (B-specific) activity; IEA:UniProtKB-EC.
DR GO; GO:0000166; F:nucleotide binding; 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 3D-structure; Cytoplasm; Direct protein sequencing; NAD;
KW Nucleotide-binding; Oxidoreductase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:8944761"
FT CHAIN 2..257
FT /note="3-alpha-hydroxysteroid dehydrogenase/carbonyl
FT reductase"
FT /id="PRO_0000054656"
FT ACT_SITE 155
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 8..13
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11007791"
FT BINDING 32
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11007791"
FT BINDING 41..42
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11007791"
FT BINDING 71
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11007791"
FT BINDING 114
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 155
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11007791"
FT BINDING 159
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11007791"
FT CONFLICT 2
FT /note="S -> D (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 9
FT /note="C -> A (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 18
FT /note="R -> C (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 26
FT /note="H -> S (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 30
FT /note="G -> S (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 3..7
FT /evidence="ECO:0007829|PDB:1FJH"
FT TURN 8..10
FT /evidence="ECO:0007829|PDB:1FJH"
FT HELIX 12..23
FT /evidence="ECO:0007829|PDB:1FJH"
FT STRAND 27..39
FT /evidence="ECO:0007829|PDB:1FJH"
FT HELIX 45..56
FT /evidence="ECO:0007829|PDB:1FJH"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:1FJH"
FT HELIX 79..86
FT /evidence="ECO:0007829|PDB:1FJH"
FT HELIX 88..102
FT /evidence="ECO:0007829|PDB:1FJH"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:1FJH"
FT STRAND 108..112
FT /evidence="ECO:0007829|PDB:1FJH"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:1FJH"
FT HELIX 122..124
FT /evidence="ECO:0007829|PDB:1FJH"
FT HELIX 128..133
FT /evidence="ECO:0007829|PDB:1FJH"
FT HELIX 136..144
FT /evidence="ECO:0007829|PDB:1FJH"
FT HELIX 150..168
FT /evidence="ECO:0007829|PDB:1FJH"
FT HELIX 170..175
FT /evidence="ECO:0007829|PDB:1FJH"
FT STRAND 179..185
FT /evidence="ECO:0007829|PDB:1FJH"
FT HELIX 220..229
FT /evidence="ECO:0007829|PDB:1FJH"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:1FJH"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:1FJH"
FT HELIX 248..252
FT /evidence="ECO:0007829|PDB:1FJH"
SQ SEQUENCE 257 AA; 26392 MW; 65B6F19444F20EFE CRC64;
MSIIVISGCA TGIGAATRKV LEAAGHQIVG IDIRDAEVIA DLSTAEGRKQ AIADVLAKCS
KGMDGLVLCA GLGPQTKVLG NVVSVNYFGA TELMDAFLPA LKKGHQPAAV VISSVASAHL
AFDKNPLALA LEAGEEAKAR AIVEHAGEQG GNLAYAGSKN ALTVAVRKRA AAWGEAGVRL
NTIAPGATET PLLQAGLQDP RYGESIAKFV PPMGRRAEPS EMASVIAFLM SPAASYVHGA
QIVIDGGIDA VMRPTQF
