CP125_MYCTO
ID CP125_MYCTO Reviewed; 433 AA.
AC P9WPP0; L0TEH2; P63709; P71856;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Steroid C26-monooxygenase {ECO:0000303|PubMed:20545858};
DE EC=1.14.15.29 {ECO:0000250|UniProtKB:P9WPP1, ECO:0000305|PubMed:20545858};
DE AltName: Full=Cholest-4-en-3-one 26-monooxygenase {ECO:0000303|PubMed:20545858};
DE AltName: Full=Cholest-4-en-3-one C26-monooxygenase [(25S)-3-oxocholest-4-en-26-oate forming] {ECO:0000250|UniProtKB:P9WPP1, ECO:0000305|PubMed:20545858};
DE AltName: Full=Cholesterol C26-monooxygenase {ECO:0000303|PubMed:20545858};
DE AltName: Full=Cholesterol C26-monooxygenase [(25S)-3beta-hydroxycholest-5-en-26-oate forming] {ECO:0000250|UniProtKB:P9WPP1, ECO:0000305|PubMed:20545858};
DE AltName: Full=Cytochrome P450 125 {ECO:0000303|PubMed:20545858};
DE AltName: Full=Steroid C27-monooxygenase {ECO:0000303|PubMed:20545858};
GN Name=cyp125; Synonyms=cyp125A1 {ECO:0000303|PubMed:20545858};
GN OrderedLocusNames=MT3649;
OS Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83331;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=12218036; DOI=10.1128/jb.184.19.5479-5490.2002;
RA Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O.,
RA Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K.,
RA Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L.,
RA Delcher A., Utterback T.R., Weidman J.F., Khouri H.M., Gill J., Mikula A.,
RA Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M.;
RT "Whole-genome comparison of Mycobacterium tuberculosis clinical and
RT laboratory strains.";
RL J. Bacteriol. 184:5479-5490(2002).
RN [2]
RP FUNCTION IN CHOLESTEROL CATABOLISM, CATALYTIC ACTIVITY, COFACTOR,
RP DISRUPTION PHENOTYPE, SUBSTRATE SPECIFICITY, AND PATHWAY.
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=20545858; DOI=10.1111/j.1365-2958.2010.07243.x;
RA Ouellet H., Guan S., Johnston J.B., Chow E.D., Kells P.M., Burlingame A.L.,
RA Cox J.S., Podust L.M., de Montellano P.R.;
RT "Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that
RT detoxifies intracellularly generated cholest-4-en-3-one.";
RL Mol. Microbiol. 77:730-742(2010).
CC -!- FUNCTION: Involved in the utilization of cholesterol as the sole carbon
CC and energy source by degrading the side chain during infection.
CC Primarily catalyzes the sequential oxidation of the terminal methyl of
CC cholest-4-en-3-one into (25S)-26-hydroxycholest-4-en-3-one (alcohol),
CC (25S)-26-oxocholest-4-en-3-one (aldehyde), to finally yield the
CC carboxylic acid (25S)-3-oxocholest-4-en-26-oate. Also able to
CC sequentially oxidize cholesterol itself, not only cholest-4-en-3-one.
CC {ECO:0000269|PubMed:20545858}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholest-4-en-3-one + 5 H(+) + 3 O2 + 6 reduced [2Fe-2S]-
CC [ferredoxin] = (25S)-3-oxocholest-4-en-26-oate + 4 H2O + 6 oxidized
CC [2Fe-2S]-[ferredoxin]; Xref=Rhea:RHEA:51564, Rhea:RHEA-COMP:10000,
CC Rhea:RHEA-COMP:10001, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16175, ChEBI:CHEBI:33737,
CC ChEBI:CHEBI:33738, ChEBI:CHEBI:71541; EC=1.14.15.29;
CC Evidence={ECO:0000250|UniProtKB:P9WPP1, ECO:0000305|PubMed:20545858};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:20545858};
CC -!- PATHWAY: Steroid metabolism; cholesterol degradation.
CC {ECO:0000305|PubMed:20545858}.
CC -!- INDUCTION: By cholesterol. {ECO:0000250|UniProtKB:P9WPP1}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene fail to grow in the
CC presence of cholesterol. {ECO:0000269|PubMed:20545858}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AE000516; AAK48008.1; -; Genomic_DNA.
DR PIR; B70677; B70677.
DR RefSeq; WP_003419304.1; NZ_KK341227.1.
DR AlphaFoldDB; P9WPP0; -.
DR SMR; P9WPP0; -.
DR BindingDB; P9WPP0; -.
DR EnsemblBacteria; AAK48008; AAK48008; MT3649.
DR KEGG; mtc:MT3649; -.
DR PATRIC; fig|83331.31.peg.3930; -.
DR HOGENOM; CLU_033716_0_0_11; -.
DR BRENDA; 1.14.15.29; 3445.
DR UniPathway; UPA01058; -.
DR Proteomes; UP000001020; Chromosome.
DR GO; GO:0036199; F:cholest-4-en-3-one 26-monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0006707; P:cholesterol catabolic process; IMP:UniProtKB.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002397; Cyt_P450_B.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00359; BP450.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 1: Evidence at protein level;
KW Cholesterol metabolism; Heme; Iron; Lipid degradation; Lipid metabolism;
KW Metal-binding; Monooxygenase; NAD; Oxidoreductase; Steroid metabolism;
KW Sterol metabolism; Virulence.
FT CHAIN 1..433
FT /note="Steroid C26-monooxygenase"
FT /id="PRO_0000426918"
FT BINDING 202
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P9WPP1"
FT BINDING 377
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P9WPP1"
SQ SEQUENCE 433 AA; 48433 MW; FCBE0594D92171F4 CRC64;
MSWNHQSVEI AVRRTTVPSP NLPPGFDFTD PAIYAERLPV AEFAELRSAA PIWWNGQDPG
KGGGFHDGGF WAITKLNDVK EISRHSDVFS SYENGVIPRF KNDIAREDIE VQRFVMLNMD
APHHTRLRKI ISRGFTPRAV GRLHDELQER AQKIAAEAAA AGSGDFVEQV SCELPLQAIA
GLLGVPQEDR GKLFHWSNEM TGNEDPEYAH IDPKASSAEL IGYAMKMAEE KAKNPADDIV
TQLIQADIDG EKLSDDEFGF FVVMLAVAGN ETTRNSITQG MMAFAEHPDQ WELYKKVRPE
TAADEIVRWA TPVTAFQRTA LRDYELSGVQ IKKGQRVVMF YRSANFDEEV FQDPFTFNIL
RNPNPHVGFG GTGAHYCIGA NLARMTINLI FNAVADHMPD LKPISAPERL RSGWLNGIKH
WQVDYTGRCP VAH
