Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DE9RA0I)

• DME Name: Beta-glucuronidase (uidA)
• Synonyms: Beta-galactosidase/beta-glucuronidase; Beta-galactosidase BgaB; GUS; JW1609; b1617; gurA; gusA; uidA
• Gene Name: uidA
• UniProt ID: BGLR_ECOLI
• INTEDE ID: DME1788
• Gene ID: 946149
• EC Number:
  EC: 3.2.1.31
  Hydrolases
  Glycosylase
  O/S-glycosyl compound glycosidase
  EC: 3.2.1.31
• Lineage:
  Species: Escherichia coli
  Kingdom: Bacteria
  Phylum: Proteobacteria
  Class: Gammaproteobacteria
  Order: Enterobacterales
  Family: Enterobacteriaceae
  Genus: Escherichia
  Species: Escherichia coli
  Subspecies: Escherichia coli K-12
• Tissue Distribution: Primarily distributed in human gut.
• Sequence:
  MLRPVETPTREIKKLDGLWAFSLDRENCGIDQRWWESALQESRAIAVPGSFNDQFADADI
  RNYAGNVWYQREVFIPKGWAGQRIVLRFDAVTHYGKVWVNNQEVMEHQGGYTPFEADVTP
  YVIAGKSVRITVCVNNELNWQTIPPGMVITDENGKKKQSYFHDFFNYAGIHRSVMLYTTP
  NTWVDDITVVTHVAQDCNHASVDWQVVANGDVSVELRDADQQVVATGQGTSGTLQVVNPH
  LWQPGEGYLYELCVTAKSQTECDIYPLRVGIRSVAVKGEQFLINHKPFYFTGFGRHEDAD
  LRGKGFDNVLMVHDHALMDWIGANSYRTSHYPYAEEMLDWADEHGIVVIDETAAVGFNLS
  LGIGFEAGNKPKELYSEEAVNGETQQAHLQAIKELIARDKNHPSVVMWSIANEPDTRPQG
  AREYFAPLAEATRKLDPTRPITCVNVMFCDAHTDTISDLFDVLCLNRYYGWYVQSGDLET
  AEKVLEKELLAWQEKLHQPIIITEYGVDTLAGLHSMYTDMWSEEYQCAWLDMYHRVFDRV
  SAVVGEQVWNFADFATSQGILRVGGNKKGIFTRDRKPKSAAFLLQKRWTGMNFGEKPQQG
  GKQ
• Function: This enzyme takes part in glucuronoside catabolic process.
• KEGG Pathway:
  Biosynthesis of secondary metabolites (ecj01110)
  Metabolic pathways (ecj01100)
  Pentose and glucuronate interconversions (ecj00040)
  Porphyrin and chlorophyll metabolism (ecj00860)

Molecular Interaction Atlas (MIA) of This DME

2 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Conjugated Estrogens	DMLT0E1	Dyspareunia	GA12	Approved	[2]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[3]

3 Investigative Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Indomethacin glucuronide	DMSBENK	N. A.	N. A.	Investigative	[4]
Ketoprofen glucuronide	DMX2FL3	N. A.	N. A.	Investigative	[5]
SN-38G	DM2UVNB	N. A.	N. A.	Investigative	[6]

The Drug Therapeutic Target (DTT) Role of This DME

• DME DTT Name: Bacterial Beta-glucuronidase (Bact uidA) DTT Info
• DME DTT Type: Preclinical

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SBX-101	DMXN4UC	Intestinal toxicities from therapy	DA94.1	Preclinical	[1]

References

• [1] Microbiome therapeutics go small molecule. Nat Rev Drug Discov. 2019 Jul;18(8):569-572.
• [2] Long-term administration of conjugated estrogen and bazedoxifene decreased murine fecal beta-glucuronidase activity without impacting overall microbiome community. Sci Rep. 2018 May 25;8(1):8166.
• [3] Involvement of beta-glucuronidase in intestinal microflora in the intestinal toxicity of the antitumor camptothecin derivative irinotecan hydrochloride (CPT-11) in rats. Cancer Res. 1996 Aug 15;56(16):3752-7.
• [4] Bidirectional interactions between indomethacin and the murine intestinal microbiota. Elife. 2015 Dec 23;4:e08973.
• [5] Bacterial beta-glucuronidase inhibition protects mice against enteropathy induced by indomethacin, ketoprofen or diclofenac: mode of action and pharmacokinetics. Xenobiotica. 2014 Jan;44(1):28-35.
• [6] Metabolism of irinotecan and its active metabolite SN-38 by intestinal microflora in rats. Oncol Rep. 2008 Oct;20(4):727-30.