ID   CP142_MYCS2             Reviewed;         401 AA.
AC   A0R4Q6;
DT   18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT   09-JAN-2007, sequence version 1.
DT   27-MAR-2024, entry version 116.
DE   RecName: Full=Steroid C26-monooxygenase {ECO:0000303|PubMed:23489718};
DE            EC=1.14.15.28 {ECO:0000269|PubMed:23489718, ECO:0000305|PubMed:25210044};
DE   AltName: Full=Cholest-4-en-3-one C26-monooxygenase {ECO:0000303|PubMed:23489718};
DE   AltName: Full=Cholest-4-en-3-one C26-monooxygenase [(25R)-3-oxocholest-4-en-26-oate forming] {ECO:0000303|PubMed:23489718};
DE   AltName: Full=Cholesterol C26-monooxygenase {ECO:0000303|PubMed:23489718};
DE   AltName: Full=Cholesterol C26-monooxygenase [(25R)-3beta-hydroxycholest-5-en-26-oate forming] {ECO:0000303|PubMed:23489718};
DE   AltName: Full=Cytochrome P450 142 {ECO:0000303|PubMed:23489718};
DE   AltName: Full=Steroid C27-monooxygenase {ECO:0000250|UniProtKB:P9WPL5};
GN   Name=cyp142 {ECO:0000303|PubMed:23489718};
GN   Synonyms=cyp142A2 {ECO:0000303|PubMed:23489718};
GN   OrderedLocusNames=MSMEG_5918 {ECO:0000312|EMBL:ABK74975.1};
OS   Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS   smegmatis).
OC   Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; Mycobacteriaceae;
OC   Mycolicibacterium.
OX   NCBI_TaxID=246196;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700084 / mc(2)155;
RA   Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA   Fraser C.M.;
RL   Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   X-RAY CRYSTALLOGRAPHY (1.69 ANGSTROMS) OF 4-401 IN COMPLEX WITH HEME,
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR,
RP   DISRUPTION PHENOTYPE, INDUCTION, SUBSTRATE SPECIFICITY, AND PATHWAY.
RC   STRAIN=ATCC 700084 / mc(2)155;
RX   PubMed=23489718; DOI=10.1111/1462-2920.12108;
RA   Garcia-Fernandez E., Frank D.J., Galan B., Kells P.M., Podust L.M.,
RA   Garcia J.L., Ortiz de Montellano P.R.;
RT   "A highly conserved mycobacterial cholesterol catabolic pathway.";
RL   Environ. Microbiol. 15:2342-2359(2013).
RN   [3]
RP   X-RAY CRYSTALLOGRAPHY (1.78 ANGSTROMS) IN COMPLEX WITH HEME, FUNCTION,
RP   CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
RX   PubMed=25210044; DOI=10.1074/jbc.m114.602771;
RA   Frank D.J., Madrona Y., Ortiz de Montellano P.R.;
RT   "Cholesterol ester oxidation by mycobacterial cytochrome P450.";
RL   J. Biol. Chem. 289:30417-30425(2014).
CC   -!- FUNCTION: Involved in the utilization of cholesterol as the sole carbon
CC       and energy source by degrading the side chain. Primarily catalyzes the
CC       sequential oxidation of the terminal methyl of cholest-4-en-3-one into
CC       (25R)-26-hydroxycholest-4-en-3-one (alcohol), (25R)-26-oxocholest-4-en-
CC       3-one (aldehyde), to finally yield the carboxylic acid (25R)-3-
CC       oxocholest-4-en-26-oate. Also able to sequentially oxidize cholesterol
CC       itself, not only cholest-4-en-3-one. {ECO:0000269|PubMed:23489718,
CC       ECO:0000269|PubMed:25210044}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=cholest-4-en-3-one + 5 H(+) + 3 O2 + 6 reduced [2Fe-2S]-
CC         [ferredoxin] = (25R)-3-oxocholest-4-en-26-oate + 4 H2O + 6 oxidized
CC         [2Fe-2S]-[ferredoxin]; Xref=Rhea:RHEA:49996, 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:71570; EC=1.14.15.28;
CC         Evidence={ECO:0000269|PubMed:23489718, ECO:0000305|PubMed:25210044};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000269|PubMed:23489718, ECO:0000269|PubMed:25210044};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=10.3 uM for cholest-4-en-3-one {ECO:0000269|PubMed:23489718};
CC         KM=39.8 uM for cholesteryl sulfate {ECO:0000269|PubMed:25210044};
CC   -!- PATHWAY: Steroid metabolism; cholesterol degradation.
CC       {ECO:0000303|PubMed:23489718}.
CC   -!- INDUCTION: By cholesterol. {ECO:0000269|PubMed:23489718}.
CC   -!- DISRUPTION PHENOTYPE: Cells lacking this gene show a slight reduction
CC       in the levels of cholest-4-en-3-one-26-oate, but the concentration of
CC       26-hydroxycholest-4-en-3-one is not measurably affected. The levels of
CC       26-hydroxycholest-4-en-3-one and cholest-4-on-3-one-26-oate are
CC       drastically reduced in cells lacking both cyp125A3 and cyp142A2.
CC       {ECO:0000269|PubMed:23489718}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; CP000480; ABK74975.1; -; Genomic_DNA.
DR   RefSeq; WP_011730892.1; NZ_SIJM01000017.1.
DR   RefSeq; YP_890144.1; NC_008596.1.
DR   PDB; 2YOO; X-ray; 1.69 A; A/B/C/D=4-401.
DR   PDB; 3ZBY; X-ray; 1.93 A; A/B/C/D/E/F=1-401.
DR   PDB; 4TRI; X-ray; 2.00 A; A/B=1-401.
DR   PDB; 4UAX; X-ray; 1.78 A; A=1-401.
DR   PDBsum; 2YOO; -.
DR   PDBsum; 3ZBY; -.
DR   PDBsum; 4TRI; -.
DR   PDBsum; 4UAX; -.
DR   AlphaFoldDB; A0R4Q6; -.
DR   SMR; A0R4Q6; -.
DR   STRING; 246196.MSMEG_5918; -.
DR   PaxDb; 246196-MSMEI_5758; -.
DR   GeneID; 66737205; -.
DR   KEGG; msm:MSMEG_5918; -.
DR   PATRIC; fig|246196.19.peg.5758; -.
DR   eggNOG; COG2124; Bacteria.
DR   OrthoDB; 5241086at2; -.
DR   BRENDA; 1.14.15.28; 3512.
DR   UniPathway; UPA01058; -.
DR   Proteomes; UP000000757; Chromosome.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR   GO; GO:0006707; P:cholesterol catabolic process; IEA:UniProtKB-UniPathway.
DR   CDD; cd11033; CYP142-like; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR002397; Cyt_P450_B.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   PANTHER; PTHR46696; P450, PUTATIVE (EUROFUNG)-RELATED; 1.
DR   PANTHER; PTHR46696:SF1; P450, PUTATIVE (EUROFUNG)-RELATED; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00359; BP450.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cholesterol metabolism; Heme; Iron; Lipid degradation;
KW   Lipid metabolism; Metal-binding; Monooxygenase; NADP; Oxidoreductase;
KW   Reference proteome; Steroid metabolism; Sterol metabolism.
FT   CHAIN           1..401
FT                   /note="Steroid C26-monooxygenase"
FT                   /id="PRO_0000438724"
FT   BINDING         343
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:0000269|PubMed:23489718,
FT                   ECO:0000269|PubMed:25210044, ECO:0007744|PDB:2YOO,
FT                   ECO:0007744|PDB:3ZBY, ECO:0007744|PDB:4TRI,
FT                   ECO:0007744|PDB:4UAX"
FT   HELIX           15..19
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           23..33
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   STRAND          35..38
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   STRAND          44..46
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           49..57
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   TURN            59..61
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   STRAND          62..64
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   STRAND          70..72
FT                   /evidence="ECO:0007829|PDB:4UAX"
FT   HELIX           78..80
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           85..93
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           94..96
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           99..103
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           106..121
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   STRAND          124..127
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           128..131
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   TURN            132..134
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           135..145
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           149..151
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           152..163
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   STRAND          168..170
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           172..198
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           204..209
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           220..235
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           238..251
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           253..261
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           263..265
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           266..277
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   STRAND          282..289
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   STRAND          291..293
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   STRAND          296..298
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   STRAND          303..307
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           308..311
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           315..318
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           339..341
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   HELIX           346..363
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   STRAND          368..371
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   STRAND          381..383
FT                   /evidence="ECO:0007829|PDB:2YOO"
FT   STRAND          390..392
FT                   /evidence="ECO:0007829|PDB:2YOO"
SQ   SEQUENCE   401 AA;  44901 MW;  9195ECA2F9D8D509 CRC64;
     MTQMLTRPDV DLVNGMFYAD GGAREAYRWM RANEPVFRDR NGLAAATTYQ AVLDAERNPE
     LFSSTGGIRP DQPGMPYMID MDDPQHLLRR KLVNAGFTRK RVMDKVDSIG RLCDTLIDAV
     CERGECDFVR DIAAPLPMAV IGDMLGVLPT ERDMLLKWSD DLVCGLSSHV DEAAIQKLMD
     TFAAYTEFTK DVITKRRAEP TDDLFSVLVN SEVEGQRMSD DEIVFETLLI LIGGDETTRH
     TLSGGTEQLL RHRDQWDALV ADVDLLPGAI EEMLRWTSPV KNMCRTLTAD TVFHGTELRA
     GEKIMLMFES ANFDESVFGD PDNFRIDRNP NSHVAFGFGT HFCLGNQLAR LELRLMTERV
     LRRLPDLRLA DDAPVPLRPA NFVSGPESMP VVFTPSAPVL A
//