CP142_MYCS2
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 03-AUG-2022, entry version 108.
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; Actinobacteria; Corynebacteriales; 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.MSMEI_5758; -.
DR PRIDE; A0R4Q6; -.
DR EnsemblBacteria; ABK74975; ABK74975; MSMEG_5918.
DR GeneID; 66737205; -.
DR KEGG; msm:MSMEG_5918; -.
DR PATRIC; fig|246196.19.peg.5758; -.
DR eggNOG; COG2124; Bacteria.
DR OMA; AGIHFCI; -.
DR OrthoDB; 816674at2; -.
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 Gene3D; 1.10.630.10; -; 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 Pfam; PF00067; p450; 1.
DR PRINTS; PR00359; BP450.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 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
