KEGG   ENZYME: 1.14.13.141Help
Entry
EC 1.14.13.141              Enzyme                                 

Name
cholest-4-en-3-one 26-monooxygenase [(25S)-3-oxocholest-4-en-26-oate forming];
CYP125;
CYP125A1;
cholest-4-en-3-one 27-monooxygenase (misleading);
cholest-4-en-3-one,NADH:oxygen oxidoreductase (26-hydroxylating);
cholest-4-en-3-one 26-monooxygenase (ambiguous)
Class
Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor
BRITE hierarchy
Sysname
cholest-4-en-3-one,NADH:oxygen oxidoreductase [(25S)-3-oxocholest-4-en-26-oate forming]
Reaction(IUBMB)
cholest-4-en-3-one + 3 NADH + 3 H+ + 3 O2 = (25S)-3-oxocholest-4-en-26-oate + 3 NAD+ + 4 H2O (overall reaction) [RN:R09859];
(1a) cholest-4-en-3-one + NADH + H+ + O2 = (25S)-26-hydroxycholest-4-en-3-one + NAD+ + H2O;
(1b) (25S)-26-hydroxycholest-4-en-3-one + NADH + H+ + O2 = (25S)-26-oxocholest-4-en-3-one + NAD+ + 2 H2O;
(1c) (25S)-26-oxocholest-4-en-3-one + NADH + H+ + O2 = (25S)-3-oxocholest-4-en-26-oate + NAD+ + H2O
Reaction(KEGG)
Substrate
cholest-4-en-3-one [CPD:C00599];
NADH [CPD:C00004];
H+ [CPD:C00080];
O2 [CPD:C00007];
(25S)-26-hydroxycholest-4-en-3-one;
(25S)-26-oxocholest-4-en-3-one
Product
(25S)-3-oxocholest-4-en-26-oate [CPD:C20839];
NAD+ [CPD:C00003];
H2O [CPD:C00001];
(25S)-26-hydroxycholest-4-en-3-one;
(25S)-26-oxocholest-4-en-3-one
Comment
This enzyme, found in several bacterial pathogens, is involved in degradation of the host's cholesterol. It catalyses the hydroxylation of the C-26 carbon, followed by oxidation of the alcohol to the carboxylic acid via the aldehyde intermediate, initiating the degradation of the alkyl side-chain of cholesterol [4]. The products are exclusively in the (25S) configuration. It is a two-component system consisting of a P-450 (heme thiolate) oxygenase (Cyp125) and a ferredoxin reductase (most likely KshB, which is also a part of EC 1.14.13.142, 3-ketosteroid 9alpha-monooxygenase). The enzyme also accepts cholesterol as a substrate. cf. EC 1.14.13.221, cholest-4-en-3-one 27-monooxygenase.
History
EC 1.14.13.141 created 2012, modified 2016
Pathway
Steroid degradation
Orthology
K15981  
cholest-4-en-3-one 26-monooxygenase
Genes
ZAL: 
MTU: 
Rv3545c(cyp125)
MTV: 
MTC: 
MRA: 
MRA_3584(cyp125)
MTF: 
MTB: 
MTK: 
MTZ: 
MTI: 
MTE: 
MTUR: 
CFBS_3761(cyp125)
MTL: 
MTO: 
MTCTRI2_3609(cyp125)
MTD: 
UDA_3545c(cyp125)
MTN: 
ERDMAN_3890(cyp125)
MTJ: 
MTUB: 
MTUC: 
MTUE: 
MTX: 
MTUH: 
MTUL: 
MTUT: 
HKBT1_3746(cyp125)
MTUU: 
HKBT2_3755(cyp125)
MTQ: 
HKBS1_3758(cyp125)
MBO: 
Mb3575c(cyp125)
MBB: 
BCG_3609c(cyp125)
MBT: 
JTY_3610(cyp125)
MBM: 
BCGMEX_3607c(cyp125)
MBK: 
MBX: 
MBZ: 
MAF: 
MAF_35570(cyp125)
MCE: 
MCAN_35561(cyp125)
MCQ: 
MCV: 
MCX: 
MCZ: 
MMIC: 
MPA: 
MAO: 
MAVI: 
MAVU: 
MAV: 
MAVD: 
MAVR: 
MAVA: 
MIT: 
MIR: 
MIA: 
MIE: 
MID: 
MYO: 
MSM: 
MSG: 
MSMEI_3443(cyp125) MSMEI_5695(cyp125) MSMEI_5834(cyp125)
MSB: 
MSN: 
MSH: 
MSA: 
MUL: 
MUL_4106(cyp125A7)
MVA: 
MGI: 
MSP: 
MAB: 
MABB: 
MMV: 
MAY: 
MABO: 
MABL: 
MAZ: 
MAK: 
MYS: 
MYC: 
MMC: 
MKM: 
MJL: 
MJD: 
JDM601_2803(cyp125A7) JDM601_3609(cyp125A7) JDM601_3682(cyp125A7) JDM601_3692(cyp125A7) JDM601_3693(cyp125A7)
MMI: 
MMAR_2783(cyp125A6) MMAR_5032(cyp125A7)
MRH: 
MMM: 
MCB: 
MLI: 
MULP_02541(cyp125A6) MULP_05284(cyp125A7)
MKN: 
MKS: 
MKI: 
MNE: 
MYV: 
MYE: 
MGO: 
MFT: 
MHAD: 
MPHL: 
MVQ: 
ASD: 
NFA: 
NCY: 
NBR: 
NNO: 
RHA: 
RER: 
REY: 
REB: 
ROP: 
ROA: 
REQ: 
RPY: 
RAV: 
GBR: 
GPO: 
GOR: 
KTR9_3902(cyp125A1)
GOQ: 
TPR: 
SMA: 
SAV_5841(cyp22)
SGR: 
SGB: 
SCB: 
SVL: 
SCT: 
SCY: 
SBH: 
SBI_07560(cyp37)
SHY: 
SHO: 
SVE: 
SDV: 
BN159_6030(cyp125)
SFI: 
SCI: 
SRC: 
SALU: 
SALL: 
STRE: 
SLD: 
STRM: 
SPRI: 
SCZ: 
SCX: 
SRW: 
NCA: 
PSIM: 
TCU: 
SRO: 
FRI: 
AMD: 
AMN: 
AMM: 
AMZ: 
AOI: 
AJA: 
AJAP_26185(cyp125)
AMQ: 
ALU: 
KAL: 
KPHY: 
STP: 
SAQ: 
AMS: 
CAI: 
ABAI: 
 » show all
Taxonomy
Reference
1  [PMID:19843222]
  Authors
Rosloniec KZ, Wilbrink MH, Capyk JK, Mohn WW, Ostendorf M, van der Geize R, Dijkhuizen L, Eltis LD
  Title
Cytochrome P450 125 (CYP125) catalyses C26-hydroxylation to initiate sterol side-chain degradation in Rhodococcus jostii RHA1.
  Journal
Mol. Microbiol. 74 (2009) 1031-43.
  Sequence
Reference
2  [PMID:19846552]
  Authors
McLean KJ, Lafite P, Levy C, Cheesman MR, Mast N, Pikuleva IA, Leys D, Munro AW
  Title
The Structure of Mycobacterium tuberculosis CYP125: molecular basis for cholesterol binding in a P450 needed for host infection.
  Journal
J. Biol. Chem. 284 (2009) 35524-33.
  Sequence
[mtu:Rv3545c]
Reference
3  [PMID:19846551]
  Authors
Capyk JK, Kalscheuer R, Stewart GR, Liu J, Kwon H, Zhao R, Okamoto S, Jacobs WR Jr, Eltis LD, Mohn WW
  Title
Mycobacterial cytochrome p450 125 (cyp125) catalyzes the terminal hydroxylation of c27 steroids.
  Journal
J. Biol. Chem. 284 (2009) 35534-42.
  Sequence
[mtu:Rv3545c]
Reference
4  [PMID:20545858]
  Authors
Ouellet H, Guan S, Johnston JB, Chow ED, Kells PM, Burlingame AL, Cox JS, Podust LM, de Montellano PR
  Title
Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies  intracellularly generated cholest-4-en-3-one.
  Journal
Mol. Microbiol. 77 (2010) 730-42.
  Sequence
[mtu:Rv3545c]
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 

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