CP125_MYCBO
ID CP125_MYCBO Reviewed; 433 AA.
AC P63710; A0A1R3Y4I9; P71856; X2BP97;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Steroid C26-monooxygenase {ECO:0000303|PubMed:19846551};
DE EC=1.14.15.29 {ECO:0000250|UniProtKB:P9WPP1, ECO:0000305|PubMed:19846551};
DE AltName: Full=Cholest-4-en-3-one 26-monooxygenase {ECO:0000303|PubMed:19846551};
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:19846551};
DE AltName: Full=Cholesterol C26-monooxygenase {ECO:0000303|PubMed:19846551};
DE AltName: Full=Cholesterol C26-monooxygenase [(25S)-3beta-hydroxycholest-5-en-26-oate forming] {ECO:0000250|UniProtKB:P9WPP1, ECO:0000305|PubMed:19846551};
DE AltName: Full=Cytochrome P450 125 {ECO:0000303|PubMed:19846551};
DE AltName: Full=Steroid C27-monooxygenase {ECO:0000303|PubMed:19846551};
GN Name=cyp125; OrderedLocusNames=BQ2027_MB3575C;
OS Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=233413;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-935 / AF2122/97;
RX PubMed=12788972; DOI=10.1073/pnas.1130426100;
RA Garnier T., Eiglmeier K., Camus J.-C., Medina N., Mansoor H., Pryor M.,
RA Duthoy S., Grondin S., Lacroix C., Monsempe C., Simon S., Harris B.,
RA Atkin R., Doggett J., Mayes R., Keating L., Wheeler P.R., Parkhill J.,
RA Barrell B.G., Cole S.T., Gordon S.V., Hewinson R.G.;
RT "The complete genome sequence of Mycobacterium bovis.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:7877-7882(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=ATCC BAA-935 / AF2122/97;
RX PubMed=28385856; DOI=10.1128/genomea.00157-17;
RA Malone K.M., Farrell D., Stuber T.P., Schubert O.T., Aebersold R.,
RA Robbe-Austerman S., Gordon S.V.;
RT "Updated reference genome sequence and annotation of Mycobacterium bovis
RT AF2122/97.";
RL Genome Announc. 5:E00157-E00157(2017).
RN [3]
RP FUNCTION IN CHOLESTEROL CATABOLISM, CATALYTIC ACTIVITY, COFACTOR,
RP DISRUPTION PHENOTYPE, SUBSTRATE SPECIFICITY, AND PATHWAY.
RX PubMed=19846551; DOI=10.1074/jbc.m109.072132;
RA Capyk J.K., Kalscheuer R., Stewart G.R., Liu J., Kwon H., Zhao R.,
RA Okamoto S., Jacobs W.R. Jr., Eltis L.D., Mohn W.W.;
RT "Mycobacterial cytochrome p450 125 (cyp125) catalyzes the terminal
RT hydroxylation of c27 steroids.";
RL J. Biol. Chem. 284:35534-35542(2009).
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:19846551}.
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:19846551};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:19846551};
CC -!- PATHWAY: Steroid metabolism; cholesterol degradation.
CC {ECO:0000305|PubMed:19846551}.
CC -!- INDUCTION: By cholesterol. {ECO:0000250|UniProtKB:P9WPP1}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this genes can transform
CC cholesterol but is unable to metabolize it sufficiently to support
CC growth. 4-cholesten-3-one is accumulated when incubated in the presence
CC of cholesterol. {ECO:0000269|PubMed:19846551}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; LT708304; SIU02202.1; -; Genomic_DNA.
DR RefSeq; NP_857214.1; NC_002945.3.
DR RefSeq; WP_003419304.1; NC_002945.4.
DR AlphaFoldDB; P63710; -.
DR SMR; P63710; -.
DR EnsemblBacteria; SIU02202; SIU02202; BQ2027_MB3575C.
DR PATRIC; fig|233413.5.peg.3918; -.
DR OMA; FQRTATQ; -.
DR UniPathway; UPA01058; -.
DR Proteomes; UP000001419; 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; IEA:UniProtKB-UniPathway.
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_0000052279"
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
