3O1D_MYCTU
ID 3O1D_MYCTU Reviewed; 563 AA.
AC P71864; L0TD13;
DT 11-JAN-2011, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 3.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=3-oxosteroid 1-dehydrogenase;
DE EC=1.3.99.4 {ECO:0000269|PubMed:18031290};
DE AltName: Full=3-keto-Delta(4)-steroid Delta(1)-dehydrogenase;
DE Short=KSDD;
DE AltName: Full=3-oxo-Delta(4)-steroid 1-dehydrogenase;
DE Short=KSTD;
GN Name=kstD; OrderedLocusNames=Rv3537;
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 KETOSTEROID DEHYDROGENASE, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=18031290; DOI=10.1042/bj20071130;
RA Knol J., Bodewits K., Hessels G.I., Dijkhuizen L., van der Geize R.;
RT "3-Keto-5alpha-steroid Delta(1)-dehydrogenase from Rhodococcus erythropolis
RT SQ1 and its orthologue in Mycobacterium tuberculosis H37Rv are highly
RT specific enzymes that function in cholesterol catabolism.";
RL Biochem. J. 410:339-346(2008).
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).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=21987574; DOI=10.1074/jbc.m111.289975;
RA Capyk J.K., Casabon I., Gruninger R., Strynadka N.C., Eltis L.D.;
RT "Activity of 3-ketosteroid 9alpha-hydroxylase (KshAB) indicates cholesterol
RT side chain and ring degradation occur simultaneously in Mycobacterium
RT tuberculosis.";
RL J. Biol. Chem. 286:40717-40724(2011).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=23425360; DOI=10.1186/1471-2180-13-43;
RA Brzezinska M., Szulc I., Brzostek A., Klink M., Kielbik M., Sulowska Z.,
RA Pawelczyk J., Dziadek J.;
RT "The role of 3-ketosteroid 1(2)-dehydrogenase in the pathogenicity of
RT Mycobacterium tuberculosis.";
RL BMC Microbiol. 13:43-43(2013).
CC -!- FUNCTION: Involved in the degradation of cholesterol (PubMed:18031290,
CC PubMed:21987574). Catalyzes the elimination of the C-1 and C-2 hydrogen
CC atoms of the A-ring from the polycyclic ring structure of 3-
CC ketosteroids (PubMed:18031290). Has a clear preference for 3-
CC ketosteroids with a saturated A-ring, displaying highest activity on
CC 5alpha-AD (5alpha-androstane-3,17-dione) and 5alpha-T (5alpha-
CC testosterone, also known as 17beta-hydroxy-5alpha-androstane-3-one)
CC (PubMed:18031290). Is also involved in the formation of 3-keto-1,4-
CC diene-steroid from 3-keto-4-ene-steroid (PubMed:21987574). Catalyzes
CC the conversion of 3-oxo-23,24-bisnorchol-4-en-22-oyl-coenzyme A
CC thioester (4-BNC-CoA) to 3-oxo-23,24-bisnorchola-1,4-dien-22-oyl-
CC coenzyme A thioester (1,4-BNC-CoA) (PubMed:21987574).
CC {ECO:0000269|PubMed:18031290, ECO:0000269|PubMed:21987574}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=A + a 3-oxosteroid = a 3-oxo-Delta(1)-steroid + AH2;
CC Xref=Rhea:RHEA:13329, ChEBI:CHEBI:13193, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:20156, ChEBI:CHEBI:47788; EC=1.3.99.4;
CC Evidence={ECO:0000269|PubMed:18031290};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=A + a 3-oxo-Delta(4)-steroid = a 3-oxo-Delta(1,4)-steroid +
CC AH2; Xref=Rhea:RHEA:53132, ChEBI:CHEBI:13193, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:47909, ChEBI:CHEBI:77166;
CC Evidence={ECO:0000269|PubMed:21987574};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxochol-4-en-22-oyl-CoA + NAD(+) = 3-oxochola-1,4-dien-22-
CC oyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:43884, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:83792,
CC ChEBI:CHEBI:83793; Evidence={ECO:0000269|PubMed:21987574};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=33 uM for 5alpha-testosterone (5alpha-T)(at pH 7.4 and 30 degrees
CC Celsius) {ECO:0000269|PubMed:18031290};
CC KM=65 uM for progesterone (at pH 7.4 and 30 degrees Celsius)
CC {ECO:0000269|PubMed:18031290};
CC KM=166 uM for 5alpha-androstane-3,17-dione (5alpha-AD)(at pH 7.4 and
CC 30 degrees Celsius) {ECO:0000269|PubMed:18031290};
CC -!- DISRUPTION PHENOTYPE: Deletion mutant is unable to use cholesterol as a
CC source of carbon and energy, and has a limited ability to multiply in
CC resting human macrophages following infection, reflecting a failure of
CC the mutant to inhibit the TLR2-dependent bactericidal activity of
CC resting macrophages. {ECO:0000269|PubMed:23425360}.
CC -!- SIMILARITY: Belongs to the FAD-dependent oxidoreductase 2 family. 3-
CC oxosteroid dehydrogenase subfamily. {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; AL123456; CCP46359.1; -; Genomic_DNA.
DR PIR; B70676; B70676.
DR RefSeq; NP_218054.1; NC_000962.3.
DR RefSeq; WP_003419253.1; NZ_NVQJ01000014.1.
DR AlphaFoldDB; P71864; -.
DR SMR; P71864; -.
DR STRING; 83332.Rv3537; -.
DR SwissLipids; SLP:000001004; -.
DR PaxDb; P71864; -.
DR DNASU; 888422; -.
DR GeneID; 888422; -.
DR KEGG; mtu:Rv3537; -.
DR TubercuList; Rv3537; -.
DR eggNOG; COG1053; Bacteria.
DR InParanoid; P71864; -.
DR OMA; HNEQMRV; -.
DR PhylomeDB; P71864; -.
DR BioCyc; MetaCyc:G185E-7814-MON; -.
DR SABIO-RK; P71864; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0047571; F:3-oxosteroid 1-dehydrogenase activity; IDA:MTBBASE.
DR GO; GO:0006707; P:cholesterol catabolic process; IDA:MTBBASE.
DR GO; GO:0006694; P:steroid biosynthetic process; IDA:UniProtKB.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR003953; FAD-binding_2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR027477; Succ_DH/fumarate_Rdtase_cat_sf.
DR Pfam; PF00890; FAD_binding_2; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF56425; SSF56425; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Lipid degradation; Lipid metabolism; Oxidoreductase;
KW Reference proteome; Steroid metabolism; Virulence.
FT CHAIN 1..563
FT /note="3-oxosteroid 1-dehydrogenase"
FT /id="PRO_0000403952"
FT BINDING 7..36
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
SQ SEQUENCE 563 AA; 60636 MW; E5548D090D7A25A8 CRC64;
MTVQEFDVVV VGSGAAGMVA ALVAAHRGLS TVVVEKAPHY GGSTARSGGG VWIPNNEVLK
RRGVRDTPEA ARTYLHGIVG EIVEPERIDA YLDRGPEMLS FVLKHTPLKM CWVPGYSDYY
PEAPGGRPGG RSIEPKPFNA RKLGADMAGL EPAYGKVPLN VVVMQQDYVR LNQLKRHPRG
VLRSMKVGAR TMWAKATGKN LVGMGRALIG PLRIGLQRAG VPVELNTAFT DLFVENGVVS
GVYVRDSHEA ESAEPQLIRA RRGVILACGG FEHNEQMRIK YQRAPITTEW TVGASANTGD
GILAAEKLGA ALDLMDDAWW GPTVPLVGKP WFALSERNSP GSIIVNMSGK RFMNESMPYV
EACHHMYGGE HGQGPGPGEN IPAWLVFDQR YRDRYIFAGL QPGQRIPSRW LDSGVIVQAD
TLAELAGKAG LPADELTATV QRFNAFARSG VDEDYHRGES AYDRYYGDPS NKPNPNLGEV
GHPPYYGAKM VPGDLGTKGG IRTDVNGRAL RDDGSIIDGL YAAGNVSAPV MGHTYPGPGG
TIGPAMTFGY LAALHIADQA GKR
