Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DEMQ20F)

• DME Name: Cytochrome P450 142A1 (cyp142)
• Synonyms: Cytochrome P450 family 142 subfamily A member 1; Cholest-4-en-3-one C26-monooxygenase 142A1; Cholest-4-en-3-one C26-monooxygenase [(25R)-3-oxocholest-4-en-26-oate forming] 142A1; Cholesterol C26-monooxygenase 142A1; Cholesterol C26-monooxygenase [(25R)-3beta-hydroxycholest-5-en-26-oate forming] 142A1; MTV023.25c; Rv3518c; Steroid C26-monooxygenase 142A1; Steroid C27-monooxygenase 142A1; cyp142A1
• Gene Name: cyp142
• UniProt ID: CP142_MYCTU
• INTEDE ID: DME1552
• Gene ID: 888282
• EC Number:
  EC: 1.14.15.28
  Oxidoreductase
  Oxygen paired donor oxidoreductase
  Iron-sulfur protein donor oxidoreductase
  EC: 1.14.15.28
• Lineage:
  Species: Mycobacterium tuberculosis
  Kingdom: Bacteria
  Phylum: Actinobacteria
  Class: Actinobacteria
  Order: Corynebacteriales
  Family: Mycobacteriaceae
  Genus: Mycobacterium
  Species: Mycobacterium tuberculosis
• Tissue Distribution: Primarily distributed in human gut.
• Sequence:
  MTEAPDVDLADGNFYASREARAAYRWMRANQPVFRDRNGLAAASTYQAVIDAERQPELFS
  NAGGIRPDQPALPMMIDMDDPAHLLRRKLVNAGFTRKRVKDKEASIAALCDTLIDAVCER
  GECDFVRDLAAPLPMAVIGDMLGVRPEQRDMFLRWSDDLVTFLSSHVSQEDFQITMDAFA
  AYNDFTRATIAARRADPTDDLVSVLVSSEVDGERLSDDELVMETLLILIGGDETTRHTLS
  GGTEQLLRNRDQWDLLQRDPSLLPGAIEEMLRWTAPVKNMCRVLTADTEFHGTALCAGEK
  MMLLFESANFDEAVFCEPEKFDVQRNPNSHLAFGFGTHFCLGNQLARLELSLMTERVLRR
  LPDLRLVADDSVLPLRPANFVSGLESMPVVFTPSPPLG
• Function: This enzyme is a P-450 heme-thiolate protein, and it is involved in degradation of the host cholesterol. The enzyme 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. The products are exclusively in the (25R) conformation. And it also accepts cholesterol as a substrate.
• KEGG Pathway:
  Microbial metabolism in diverse environments (mtu01120)
  Steroid degradation (mtu00984)

Molecular Interaction Atlas (MIA) of This DME

1 Clinical Trial Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ANW-32821	DMMJOZD	N. A.	N. A.	Phase 2	[1]

References

• [1] Function, essentiality, and expression of cytochrome P450 enzymes and their cognate redox partners in Mycobacterium tuberculosis: are they drug targets? Appl Microbiol Biotechnol. 2019 May;103(9):3597-3614.