Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTICX3S)

• DTT Name: Bacterial UDP-N-acetylglucosamine carboxyvinyltransferase (Bact murA)
• Synonyms: UDP-N-acetylglucosamine enolpyruvyl transferase; UDP-GlcNAcenolpyruvyl transferase; MurA protein; MurA; Enoylpyruvate transferase; EPT
• Gene Name: Bact murA
• DTT Type: Successful target; [1]
• Related Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• BioChemical Class: Alkyl aryl transferase
• UniProt ID: MURA_ECOLI
• TTD ID: T24634
• Sequence:
  MDKFRVQGPTKLQGEVTISGAKNAALPILFAALLAEEPVEIQNVPKLKDVDTSMKLLSQL
  GAKVERNGSVHIDARDVNVFCAPYDLVKTMRASIWALGPLVARFGQGQVSLPGGCTIGAR
  PVDLHISGLEQLGATIKLEEGYVKASVDGRLKGAHIVMDKVSVGATVTIMCAATLAEGTT
  IIENAAREPEIVDTANFLITLGAKISGQGTDRIVIEGVERLGGGVYRVLPDRIETGTFLV
  AAAISRGKIICRNAQPDTLDAVLAKLRDAGADIEVGEDWISLDMHGKRPKAVNVRTAPHP
  AFPTDMQAQFTLLNLVAEGTGFITETVFENRFMHVPELSRMGAHAEIESNTVICHGVEKL
  SGAQVMATDLRASASLVLAGCIAEGTTVVDRIYHIDRGYERIEDKLRALGANIERVKGE
• Function: Cell wall formation. Adds enolpyruvyl to UDP-n- acetylglucosamine. Target for the antibiotic phosphomycin.
• KEGG Pathway:
  Amino sugar and nucleotide sugar metabolism (ecj00520)
  Peptidoglycan biosynthesis (ecj00550)
  Metabolic pathways (ecj01100)
  Biosynthesis of nucleotide sugars (ecj01250)
• BioCyc Pathway:
  MetaCyc:UDPNACETYLGLUCOSAMENOLPYRTRANS-MON
  EcoCyc:UDPNACETYLGLUCOSAMENOLPYRTRANS-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fosfomycin	DMVGPMX	Bacterial infection	1A00-1C4Z	Approved	[1], [2], [3], [4]

9 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aminomethylcyclohexane	DMNX9FC	Discovery agent	N.A.	Investigative	[5]
CNICIN	DMEVM0J	Discovery agent	N.A.	Investigative	[6]
Cyclohexylammonium Ion	DMYQH2N	Discovery agent	N.A.	Investigative	[5]
CYNAROPICRIN	DMG0PHU	Discovery agent	N.A.	Investigative	[6]
EUPATORIOPICRIN	DM068CY	Discovery agent	N.A.	Investigative	[6]
L-Iso-Aspartate	DM26AB4	Discovery agent	N.A.	Investigative	[5]
RWJ-140998	DMP7SI9	Gram-positive bacterial infection	1B74-1G40	Investigative	[7]
RWJ-3981	DMBVLCQ	Gram-positive bacterial infection	1B74-1G40	Investigative	[7]
Uridine-Diphosphate-N-Acetylglucosamine	DMEQSTP	Discovery agent	N.A.	Investigative	[8]

References

• [1] Evidence that the fosfomycin target Cys115 in UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is essential for product release. J Biol Chem. 2005 Feb 4;280(5):3757-63.
• [2] Conditional lethal amber mutations in essential Escherichia coli genes. J Bacteriol. 2004 May;186(9):2673-81.
• [3] In vitro and in vivo functional activity of Chlamydia MurA, a UDP-N-acetylglucosamine enolpyruvyl transferase involved in peptidoglycan synthesis and fosfomycin resistance. J Bacteriol. 2003 Feb;185(4):1218-28.
• [4] Lysine 22 in UDP-N-acetylglucosamine enolpyruvyl transferase from Enterobacter cloacae is crucial for enzymatic activity and the formation of covalent adducts with the substrate phosphoenolpyruvate and the antibiotic fosfomycin. Biochemistry. 1999 Oct 5;38(40):13162-9.
• [5] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [6] Sesquiterpene lactones are potent and irreversible inhibitors of the antibacterial target enzyme MurA. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5605-9.
• [7] Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98.
• [8] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.