CP125_MYCS2
ID CP125_MYCS2 Reviewed; 427 AA.
AC A0R4Y3; I7G9K1;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Steroid C26-monooxygenase {ECO:0000303|PubMed:23489718};
DE EC=1.14.15.29 {ECO:0000250|UniProtKB:P9WPP1, ECO:0000305|PubMed:23489718};
DE AltName: Full=Cholest-4-en-3-one C26-monooxygenase {ECO:0000303|PubMed:23489718};
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:23489718};
DE AltName: Full=Cholesterol C26-monooxygenase {ECO:0000303|PubMed:23489718};
DE AltName: Full=Cholesterol C26-monooxygenase [(25S)-3beta-hydroxycholest-5-en-26-oate forming] {ECO:0000250|UniProtKB:P9WPP1, ECO:0000305|PubMed:23489718};
DE AltName: Full=Cytochrome P450 125 {ECO:0000303|PubMed:23489718};
DE AltName: Full=Steroid C27-monooxygenase {ECO:0000250|UniProtKB:P9WPP1};
GN Name=cyp125 {ECO:0000303|PubMed:23489718};
GN Synonyms=cyp125A3 {ECO:0000303|PubMed:23489718};
GN OrderedLocusNames=MSMEG_5995 {ECO:0000312|EMBL:ABK74881.1};
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20;
RA Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C.,
RA Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.;
RT "Interrupted coding sequences in Mycobacterium smegmatis: authentic
RT mutations or sequencing errors?";
RL Genome Biol. 8:R20.1-R20.9(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=18955433; DOI=10.1101/gr.081901.108;
RA Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M.,
RA Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.;
RT "Ortho-proteogenomics: multiple proteomes investigation through orthology
RT and a new MS-based protocol.";
RL Genome Res. 19:128-135(2009).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH HEME, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, INDUCTION,
RP DISRUPTION PHENOTYPE, SUBSTRATE SPECIFICITY, AND PATHWAY.
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 [5] {ECO:0007744|PDB:5DQN}
RP X-RAY CRYSTALLOGRAPHY (2.26 ANGSTROMS) IN COMPLEX WITH HEME, AND COFACTOR.
RX PubMed=26522442; DOI=10.1021/acs.biochem.5b01029;
RA Frank D.J., Waddling C.A., La M., Ortiz de Montellano P.R.;
RT "Cytochrome P450 125A4, the Third Cholesterol C-26 Hydroxylase from
RT Mycobacterium smegmatis.";
RL Biochemistry 54:6909-6916(2015).
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 (25S)-26-hydroxycholest-4-en-3-one (alcohol), (25S)-26-oxocholest-4-en-
CC 3-one (aldehyde), to finally yield the carboxylic acid (25S)-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 -!- 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:23489718};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:23489718, ECO:0000269|PubMed:26522442};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=14 uM for cholest-4-en-3-one {ECO:0000269|PubMed:23489718};
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 lower accumulation
CC of 26-hydroxycholest-4-en-3-one and cholest-4-en-3-one-26-oate when
CC compared with the wild-type and display a strong induction of cyp142A2.
CC The levels of 26-hydroxycholest-4-en-3-one and cholest-4-on-3-one-26-
CC oate are drastically reduced in cells lacking both cyp125A3 and
CC cyp142A2. {ECO:0000269|PubMed:23489718}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; CP000480; ABK74881.1; -; Genomic_DNA.
DR EMBL; CP001663; AFP42267.1; -; Genomic_DNA.
DR RefSeq; WP_011730960.1; NZ_SIJM01000017.1.
DR RefSeq; YP_890221.1; NC_008596.1.
DR PDB; 4APY; X-ray; 2.00 A; A=1-427.
DR PDB; 5DQN; X-ray; 2.26 A; A=1-426.
DR PDBsum; 4APY; -.
DR PDBsum; 5DQN; -.
DR AlphaFoldDB; A0R4Y3; -.
DR SMR; A0R4Y3; -.
DR STRING; 246196.MSMEI_5834; -.
DR EnsemblBacteria; ABK74881; ABK74881; MSMEG_5995.
DR EnsemblBacteria; AFP42267; AFP42267; MSMEI_5834.
DR GeneID; 66737280; -.
DR KEGG; msg:MSMEI_5834; -.
DR KEGG; msm:MSMEG_5995; -.
DR PATRIC; fig|246196.19.peg.5831; -.
DR eggNOG; COG2124; Bacteria.
DR OMA; QRFILIN; -.
DR OrthoDB; 816674at2; -.
DR BRENDA; 1.14.15.29; 3512.
DR UniPathway; UPA01058; -.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; 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 3D-structure; Cholesterol metabolism; Heme; Iron; Lipid degradation;
KW Lipid metabolism; Metal-binding; Monooxygenase; NAD; Oxidoreductase;
KW Reference proteome; Steroid metabolism; Sterol metabolism.
FT CHAIN 1..427
FT /note="Steroid C26-monooxygenase"
FT /id="PRO_0000438723"
FT BINDING 360
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:0007744|PDB:4APY, ECO:0007744|PDB:5DQN"
FT CONFLICT 1
FT /note="M -> MHFEERTPM (in Ref. 2; AFP42267)"
FT /evidence="ECO:0000305"
FT STRAND 4..6
FT /evidence="ECO:0007829|PDB:5DQN"
FT HELIX 15..20
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 24..33
FT /evidence="ECO:0007829|PDB:4APY"
FT STRAND 35..40
FT /evidence="ECO:0007829|PDB:4APY"
FT TURN 46..48
FT /evidence="ECO:0007829|PDB:4APY"
FT STRAND 51..56
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 59..67
FT /evidence="ECO:0007829|PDB:4APY"
FT TURN 69..71
FT /evidence="ECO:0007829|PDB:4APY"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:4APY"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 89..93
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 99..101
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 106..114
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 120..124
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 127..142
FT /evidence="ECO:0007829|PDB:4APY"
FT STRAND 145..148
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 149..152
FT /evidence="ECO:0007829|PDB:4APY"
FT TURN 153..155
FT /evidence="ECO:0007829|PDB:5DQN"
FT HELIX 156..166
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 173..183
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 196..216
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 222..227
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 238..251
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 254..269
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 271..280
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 285..293
FT /evidence="ECO:0007829|PDB:4APY"
FT STRAND 298..305
FT /evidence="ECO:0007829|PDB:4APY"
FT STRAND 307..309
FT /evidence="ECO:0007829|PDB:4APY"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:4APY"
FT STRAND 319..323
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 324..327
FT /evidence="ECO:0007829|PDB:4APY"
FT TURN 331..333
FT /evidence="ECO:0007829|PDB:4APY"
FT STRAND 334..336
FT /evidence="ECO:0007829|PDB:4APY"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:4APY"
FT HELIX 363..380
FT /evidence="ECO:0007829|PDB:4APY"
FT STRAND 385..388
FT /evidence="ECO:0007829|PDB:4APY"
FT STRAND 396..398
FT /evidence="ECO:0007829|PDB:4APY"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:4APY"
FT STRAND 405..412
FT /evidence="ECO:0007829|PDB:4APY"
SQ SEQUENCE 427 AA; 47106 MW; D1C6EE17D397B8FD CRC64;
MPTPNIPSDF DFLDATLNLE RLPVEELAEL RKSEPIHWVD VPGGTGGFGD KGYWLVTKHA
DVKEVSRRSD VFGSSPDGAI PVWPQDMTRE AVDLQRAVLL NMDAPQHTRL RKIISRGFTP
RAIGRLEDEL RSRAQKIAQT AAAQGAGDFV EQVSCELPLQ AIAELLGVPQ DDRDKLFRWS
NEMTAGEDPE YADVDPAMSS FELISYAMKM AEERAVNPTE DIVTKLIEAD IDGEKLSDDE
FGFFVVMLAV AGNETTRNSI THGMIAFAQN PDQWELYKKE RPETAADEIV RWATPVSAFQ
RTALEDVELG GVQIKKGQRV VMSYRSANFD EEVFEDPHTF NILRSPNPHV GFGGTGAHYC
IGANLARMTI NLIFNAIADN MPDLKPIGAP ERLKSGWLNG IKHWQVDYTG AGKASVSGAP
GTCPVAH
