Legends: 1, Iron (heme axial ligand). {ECO:0000244|PDB:2YOO, ECO:0000244|PDB:3ZBY, ECO:0000244|PDB:4TRI, ECO:0000244|PDB:4UAX, ECO:0000269|PubMed:23489718, ECO:0000269|PubMed:25210044}; 2, ipat:CYTOCHROME_P450 [T]; 3, HELIX {ECO:0000244|PDB:2YOO}; 4, STRAND {ECO:0000244|PDB:2YOO}; 5, TURN {ECO:0000244|PDB:2YOO}; 6, STRAND {ECO:0000244|PDB:4UAX}.
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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 10-MAY-2017, entry version 84.
DE RecName: Full=Steroid C26-monooxygenase {ECO:0000303|PubMed:23489718};
DE EC=1.14.13.221 {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 Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium.
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
CC carbon and energy source by degrading the side chain. Primarily
CC catalyzes the sequential oxidation of the terminal methyl of
CC cholest-4-en-3-one into (25R)-26-hydroxycholest-4-en-3-one
CC (alcohol), (25R)-26-oxocholest-4-en-3-one (aldehyde), to finally
CC yield the carboxylic acid (25R)-3-oxocholest-4-en-26-oate. Also
CC able to sequentially oxidize cholesterol itself, not only cholest-
CC 4-en-3-one. {ECO:0000269|PubMed:23489718,
CC ECO:0000269|PubMed:25210044}.
CC -!- CATALYTIC ACTIVITY: Cholest-4-en-3-one + 3 NADPH + 3 O(2) = (25R)-
CC 3-oxocholest-4-en-26-oate + 3 NADP(+) + 4 H(2)O.
CC {ECO:0000269|PubMed:23489718, ECO:0000305|PubMed:25210044}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:23489718,
CC 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
CC {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
CC reduction in the levels of cholest-4-en-3-one-26-oate, but the
CC concentration of 26-hydroxycholest-4-en-3-one is not measurably
CC affected. The levels of 26-hydroxycholest-4-en-3-one and cholest-
CC 4-on-3-one-26-oate are drastically reduced in cells lacking both
CC cyp125A3 and cyp142A2. {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_CP009494.1.
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 ProteinModelPortal; A0R4Q6; -.
DR SMR; A0R4Q6; -.
DR STRING; 246196.MSMEG_5918; -.
DR EnsemblBacteria; ABK74975; ABK74975; MSMEG_5918.
DR GeneID; 4533135; -.
DR KEGG; msb:LJ00_29265; -.
DR KEGG; msm:MSMEG_5918; -.
DR PATRIC; 18084077; VBIMycSme59918_5758.
DR eggNOG; ENOG410719E; Bacteria.
DR eggNOG; ENOG410YPZF; LUCA.
DR HOGENOM; HOG000243680; -.
DR KO; K16046; -.
DR OMA; AYAWMRA; -.
DR OrthoDB; POG091H0API; -.
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 InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002397; Cyt_P450_B.
DR InterPro; IPR017972; Cyt_P450_CS.
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; Complete proteome; Heme; Iron;
KW Lipid degradation; Lipid metabolism; Metal-binding; Monooxygenase;
KW NADP; Oxidoreductase; Reference proteome; Steroid metabolism;
KW Sterol metabolism.
FT CHAIN 1 401 Steroid C26-monooxygenase.
FT /FTId=PRO_0000438724.
FT METAL 343 343 Iron (heme axial ligand).
FT {ECO:0000244|PDB:2YOO,
FT ECO:0000244|PDB:3ZBY,
FT ECO:0000244|PDB:4TRI,
FT ECO:0000244|PDB:4UAX,
FT ECO:0000269|PubMed:23489718,
FT ECO:0000269|PubMed:25210044}.
FT HELIX 15 19 {ECO:0000244|PDB:2YOO}.
FT HELIX 23 33 {ECO:0000244|PDB:2YOO}.
FT STRAND 35 38 {ECO:0000244|PDB:2YOO}.
FT STRAND 44 46 {ECO:0000244|PDB:2YOO}.
FT HELIX 49 57 {ECO:0000244|PDB:2YOO}.
FT TURN 59 61 {ECO:0000244|PDB:2YOO}.
FT STRAND 62 64 {ECO:0000244|PDB:2YOO}.
FT STRAND 70 72 {ECO:0000244|PDB:4UAX}.
FT HELIX 78 80 {ECO:0000244|PDB:2YOO}.
FT HELIX 85 93 {ECO:0000244|PDB:2YOO}.
FT HELIX 94 96 {ECO:0000244|PDB:2YOO}.
FT HELIX 99 103 {ECO:0000244|PDB:2YOO}.
FT HELIX 106 121 {ECO:0000244|PDB:2YOO}.
FT STRAND 124 127 {ECO:0000244|PDB:2YOO}.
FT HELIX 128 131 {ECO:0000244|PDB:2YOO}.
FT TURN 132 134 {ECO:0000244|PDB:2YOO}.
FT HELIX 135 145 {ECO:0000244|PDB:2YOO}.
FT HELIX 149 151 {ECO:0000244|PDB:2YOO}.
FT HELIX 152 163 {ECO:0000244|PDB:2YOO}.
FT STRAND 168 170 {ECO:0000244|PDB:2YOO}.
FT HELIX 172 198 {ECO:0000244|PDB:2YOO}.
FT HELIX 204 209 {ECO:0000244|PDB:2YOO}.
FT HELIX 220 235 {ECO:0000244|PDB:2YOO}.
FT HELIX 238 251 {ECO:0000244|PDB:2YOO}.
FT HELIX 253 261 {ECO:0000244|PDB:2YOO}.
FT HELIX 263 265 {ECO:0000244|PDB:2YOO}.
FT HELIX 266 277 {ECO:0000244|PDB:2YOO}.
FT STRAND 282 289 {ECO:0000244|PDB:2YOO}.
FT STRAND 291 293 {ECO:0000244|PDB:2YOO}.
FT STRAND 296 298 {ECO:0000244|PDB:2YOO}.
FT STRAND 303 307 {ECO:0000244|PDB:2YOO}.
FT HELIX 308 311 {ECO:0000244|PDB:2YOO}.
FT HELIX 315 318 {ECO:0000244|PDB:2YOO}.
FT HELIX 339 341 {ECO:0000244|PDB:2YOO}.
FT HELIX 346 363 {ECO:0000244|PDB:2YOO}.
FT STRAND 368 371 {ECO:0000244|PDB:2YOO}.
FT STRAND 381 383 {ECO:0000244|PDB:2YOO}.
FT STRAND 390 392 {ECO:0000244|PDB:2YOO}.
CC --------------------------------------------------------------------------
CC The following FT lines are automated annotations from the MyHits database.
CC --------------------------------------------------------------------------
FT MYHIT 336 345 ipat:CYTOCHROME_P450 [T]
FT MYHIT 174 364 ipfam:p450 [T]
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
//
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