Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DE4OGUF)

• DME Name: Cytochrome P450 102A1 (cyp102)
• Synonyms: Cytochrome P450 family 102 subfamily A member 1; Flavocytochrome P450 102A1; P450 102A1; cyp102A1
• Gene Name: cyp102A1
• UniProt ID: CPXB_BACMB
• INTEDE ID: DME1075
• Gene ID: 29911283
• EC Number:
  EC: 1.14.14.1
  Oxidoreductase
  Oxygen paired donor oxidoreductase
  Flavin/flavoprotein donor oxidoreductase
  EC: 1.14.14.1
• Lineage:
  Species: Bacillus megaterium
  Kingdom: Bacteria
  Phylum: Firmicutes
  Class: Bacilli
  Order: Bacillales
  Family: Bacillaceae
  Genus: Bacillus
  Species: Bacillus megaterium
• Tissue Distribution: Primarily distributed in human gut.
• Sequence:
  MTIKEMPQPKTFGELKNLPLLNTDKPVQALMKIADELGEIFKFEAPGRVTRYLSSQRLIK
  EACDESRFDKNLSQALKFVRDFAGDGLFTSWTHEKNWKKAHNILLPSFSQQAMKGYHAMM
  VDIAVQLVQKWERLNADEHIEVPEDMTRLTLDTIGLCGFNYRFNSFYRDQPHPFITSMVR
  ALDEAMNKLQRANPDDPAYDENKRQFQEDIKVMNDLVDKIIADRKASGEQSDDLLTHMLN
  GKDPETGEPLDDENIRYQIITFLIAGHETTSGLLSFALYFLVKNPHVLQKAAEEAARVLV
  DPVPSYKQVKQLKYVGMVLNEALRLWPTAPAFSLYAKEDTVLGGEYPLEKGDELMVLIPQ
  LHRDKTIWGDDVEEFRPERFENPSAIPQHAFKPFGNGQRACIGQQFALHEATLVLGMMLK
  HFDFEDHTNYELDIKETLTLKPEGFVVKAKSKKIPLGGIPSPSTEQSAKKVRKKAENAHN
  TPLLVLYGSNMGTAEGTARDLADIAMSKGFAPQVATLDSHAGNLPREGAVLIVTASYNGH
  PPDNAKQFVDWLDQASADEVKGVRYSVFGCGDKNWATTYQKVPAFIDETLAAKGAENIAD
  RGEADASDDFEGTYEEWREHMWSDVAAYFNLDIENSEDNKSTLSLQFVDSAADMPLAKMH
  GAFSTNVVASKELQQPGSARSTRHLEIELPKEASYQEGDHLGVIPRNYEGIVNRVTARFG
  LDASQQIRLEAEEEKLAHLPLAKTVSVEELLQYVELQDPVTRTQLRAMAAKTVCPPHKVE
  LEALLEKQAYKEQVLAKRLTMLELLEKYPACEMKFSEFIALLPSIRPRYYSISSSPRVDE
  KQASITVSVVSGEAWSGYGEYKGIASNYLAELQEGDTITCFISTPQSEFTLPKDPETPLI
  MVGPGTGVAPFRGFVQARKQLKEQGQSLGEAHLYFGCRSPHEDYLYQEELENAQSEGIIT
  LHTAFSRMPNQPKTYVQHVMEQDGKKLIELLDQGAHFYICGDGSQMAPAVEATLMKSYAD
  VHQVSEADARLWLQQLEEKGRYAKDVWAG
• Function: This enzyme is P-450 heme-thiolate protein, acting on a wide range of substrates including many xenobiotics, steroids, fatty acids, vitamins and prostaglandins; reactions catalysed include hydroxylation, epoxidation, N-oxidation, sulfooxidation, N-, S- and O-dealkylations, desulfation, deamination, and reduction of azo, nitro and N-oxide groups.
• KEGG Pathway:
  Aminobenzoate degradation (bmeg00627)
  Fatty acid degradation (bmeg00071)
  Microbial metabolism in diverse environments (bmeg01120)
  Tryptophan metabolism (bmeg00380)

Molecular Interaction Atlas (MIA) of This DME

10 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetaminophen	DMUIE76	Pain	MG30-MG3Z	Approved	[1]
Amodiaquine	DME4RA8	Malaria	1F40-1F45	Approved	[1]
Buspirone	DMBS632	Anxiety disorder	6B00-6B0Z	Approved	[1], [2]
Chlorzoxazone	DMCYVDT	Acute pain	MG31	Approved	[3], [1]
Dextromethorphan	DMUDJZM	Cough	MD12	Approved	[1]
Diclofenac	DMPIHLS	Osteoarthritis	FA00-FA05	Approved	[4]
Meclofenamic acid	DM05FXR	Ankylosing spondylitis	FA92.0	Approved	[4]
Mefenamic acid	DMK7HFI	Dysmenorrhea	GA34.3	Approved	[4]
Nifedipine	DMSVOZT	Angina pectoris	BA40	Approved	[3], [1]
Propranolol	DM79NTF	Migraine	8A80	Approved	[2]

1 Clinical Trial Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GEA-6414	DM8J0MK	Parkinson disease	8A00.0	Phase 1/2	[4]

4 Investigative Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aniline	DMLCAR9	Discovery agent	N.A.	Investigative	[3], [1]
Benzyloxyresorufin	DM26SR7	Discovery agent	N.A.	Investigative	[1]
Methylenedioxymethamphetamine	DMYVU47	Discovery agent	N.A.	Investigative	[1]
Mononitrophenol	DM4QO9G	Discovery agent	N.A.	Investigative	[3], [1]

References

• [1] The bacterial P450 BM3: a prototype for a biocatalyst with human P450 activities. Trends Biotechnol. 2007 Jul;25(7):289-98.
• [2] acillus megaterium SF185 spores exert protective effects against oxidative stress in vivo and in vitro. Sci Rep. 2019 Aug 19;9(1):12082.
• [3] Wild-type CYP102A1 as a biocatalyst: turnover of drugs usually metabolised by human liver enzymes. J Biol Inorg Chem. 2007 Mar;12(3):313-23.
• [4] Both reactivity and accessibility are important in cytochrome P450 metabolism: a combined DFT and MD study of fenamic acids in BM3 mutants. J Chem Inf Model. 2019 Feb 25;59(2):743-753.