3BHS_MYCTU
ID 3BHS_MYCTU Reviewed; 370 AA.
AC P9WQP7; L0T7C3; O53454; Q7D8U6;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase;
DE AltName: Full=Cholesterol dehydrogenase;
DE Includes:
DE RecName: Full=3-beta-hydroxy-Delta(5)-steroid dehydrogenase;
DE Short=3-beta-HSD;
DE Short=3BHSD;
DE EC=1.1.1.145 {ECO:0000269|PubMed:17630785};
DE AltName: Full=3-beta hydroxysterol dehydrogenase;
DE AltName: Full=3-beta-hydroxy-5-ene steroid dehydrogenase;
DE AltName: Full=Progesterone reductase;
DE Includes:
DE RecName: Full=Steroid Delta-isomerase;
DE EC=5.3.3.1 {ECO:0000269|PubMed:17630785};
DE AltName: Full=Delta-5-3-ketosteroid isomerase;
GN OrderedLocusNames=Rv1106c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION AS A 3BETA-HYDROXYSTEROL DEHYDROGENASE AND ISOMERASE, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, DISRUPTION
RP PHENOTYPE, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=17630785; DOI=10.1021/bi700688x;
RA Yang X., Dubnau E., Smith I., Sampson N.S.;
RT "Rv1106c from Mycobacterium tuberculosis is a 3beta-hydroxysteroid
RT dehydrogenase.";
RL Biochemistry 46:9058-9067(2007).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC -!- FUNCTION: 3-beta-HSD is a bifunctional enzyme, that catalyzes the
CC oxidation and isomerization of cholesterol, pregnenolone, and
CC dehydroepiandrosterone (DHEA) into cholest-4-en-3-one, progesterone,
CC and androsterone, respectively. {ECO:0000269|PubMed:17630785}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3beta-hydroxy-Delta(5)-steroid + NAD(+) = a 3-oxo-Delta(5)-
CC steroid + H(+) + NADH; Xref=Rhea:RHEA:24076, ChEBI:CHEBI:1722,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:47907, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.1.1.145;
CC Evidence={ECO:0000269|PubMed:17630785};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol + NAD(+) = cholest-5-en-3-one + H(+) + NADH;
CC Xref=Rhea:RHEA:35459, ChEBI:CHEBI:15378, ChEBI:CHEBI:16113,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:63906;
CC Evidence={ECO:0000269|PubMed:17630785};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35460;
CC Evidence={ECO:0000269|PubMed:17630785};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + pregnenolone = H(+) + NADH + pregn-5-ene-3,20-dione;
CC Xref=Rhea:RHEA:43924, ChEBI:CHEBI:15378, ChEBI:CHEBI:16581,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:63837;
CC Evidence={ECO:0000269|PubMed:17630785};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43925;
CC Evidence={ECO:0000269|PubMed:17630785};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxyandrost-5-en-17-one + NAD(+) = androst-5-ene-
CC 3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:43932, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28689, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:83865; EC=1.1.1.145;
CC Evidence={ECO:0000269|PubMed:17630785};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43933;
CC Evidence={ECO:0000269|PubMed:17630785};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3-oxo-Delta(5)-steroid = a 3-oxo-Delta(4)-steroid;
CC Xref=Rhea:RHEA:14709, ChEBI:CHEBI:47907, ChEBI:CHEBI:47909;
CC EC=5.3.3.1; Evidence={ECO:0000269|PubMed:17630785};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholest-5-en-3-one = cholest-4-en-3-one; Xref=Rhea:RHEA:32187,
CC ChEBI:CHEBI:16175, ChEBI:CHEBI:63906; EC=5.3.3.1;
CC Evidence={ECO:0000269|PubMed:17630785};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32188;
CC Evidence={ECO:0000269|PubMed:17630785};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=pregn-5-ene-3,20-dione = progesterone; Xref=Rhea:RHEA:43928,
CC ChEBI:CHEBI:17026, ChEBI:CHEBI:63837;
CC Evidence={ECO:0000269|PubMed:17630785};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43929;
CC Evidence={ECO:0000269|PubMed:17630785};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=androst-5-ene-3,17-dione = androst-4-ene-3,17-dione;
CC Xref=Rhea:RHEA:43936, ChEBI:CHEBI:16422, ChEBI:CHEBI:83865;
CC Evidence={ECO:0000269|PubMed:17630785};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43937;
CC Evidence={ECO:0000269|PubMed:17630785};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA, zinc, silver, copper, and
CC activated by magnesium and calcium. A competitive inhibition is
CC observed with NAD at concentrations higher than 5.6 mM, and with
CC trilostane (3,17-dihydroxy-4,5-epoxyandrost-2-ene-2-carbonitrile).
CC {ECO:0000269|PubMed:17630785}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is between 8.5-9.5. No catalytic activity is detected
CC below pH 7.5. {ECO:0000269|PubMed:17630785};
CC -!- PATHWAY: Lipid metabolism; steroid biosynthesis.
CC -!- SUBUNIT: Monomer. {ECO:0000305|PubMed:17630785}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17630785}.
CC -!- DISRUPTION PHENOTYPE: Disruption reduces the cholesterol oxidation
CC activity at least 90-fold. {ECO:0000269|PubMed:17630785}.
CC -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
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DR EMBL; AL123456; CCP43859.1; -; Genomic_DNA.
DR PIR; H70897; H70897.
DR RefSeq; NP_215622.1; NC_000962.3.
DR RefSeq; WP_003405840.1; NZ_NVQJ01000021.1.
DR AlphaFoldDB; P9WQP7; -.
DR SMR; P9WQP7; -.
DR STRING; 83332.Rv1106c; -.
DR BindingDB; P9WQP7; -.
DR ChEMBL; CHEMBL1744528; -.
DR SwissLipids; SLP:000001012; -.
DR PaxDb; P9WQP7; -.
DR PRIDE; P9WQP7; -.
DR DNASU; 886004; -.
DR GeneID; 45425080; -.
DR GeneID; 886004; -.
DR KEGG; mtu:Rv1106c; -.
DR TubercuList; Rv1106c; -.
DR eggNOG; COG0451; Bacteria.
DR OMA; WGPGDTQ; -.
DR PhylomeDB; P9WQP7; -.
DR BioCyc; MetaCyc:G185E-5271-MON; -.
DR BRENDA; 1.1.1.145; 3445.
DR UniPathway; UPA00062; -.
DR PRO; PR:P9WQP7; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; IDA:MTBBASE.
DR GO; GO:0102294; F:cholesterol dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0070403; F:NAD+ binding; IDA:MTBBASE.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0004769; F:steroid delta-isomerase activity; IDA:MTBBASE.
DR GO; GO:0030283; F:testosterone dehydrogenase [NAD(P)] activity; IDA:UniProtKB.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006694; P:steroid biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0008202; P:steroid metabolic process; IDA:MTBBASE.
DR InterPro; IPR002225; 3Beta_OHSteriod_DH/Estase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01073; 3Beta_HSD; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Isomerase; Lipid degradation; Lipid metabolism;
KW Multifunctional enzyme; NAD; Oxidoreductase; Reference proteome;
KW Steroid metabolism.
FT CHAIN 1..370
FT /note="3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-
FT isomerase"
FT /id="PRO_0000403957"
FT ACT_SITE 158
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 162
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
SQ SEQUENCE 370 AA; 40742 MW; B2A93EC32AFEEA0B CRC64;
MLRRMGDASL TTELGRVLVT GGAGFVGANL VTTLLDRGHW VRSFDRAPSL LPAHPQLEVL
QGDITDADVC AAAVDGIDTI FHTAAIIELM GGASVTDEYR QRSFAVNVGG TENLLHAGQR
AGVQRFVYTS SNSVVMGGQN IAGGDETLPY TDRFNDLYTE TKVVAERFVL AQNGVDGMLT
CAIRPSGIWG NGDQTMFRKL FESVLKGHVK VLVGRKSARL DNSYVHNLIH GFILAAAHLV
PDGTAPGQAY FINDAEPINM FEFARPVLEA CGQRWPKMRI SGPAVRWVMT GWQRLHFRFG
FPAPLLEPLA VERLYLDNYF SIAKARRDLG YEPLFTTQQA LTECLPYYVS LFEQMKNEAR
AEKTAATVKP
