DT-Web

DB00828 - Fosfomycin


Identification
Name Fosfomycin
Accession Number DB00828 (APRD00987)
Type small molecule
Description An antibiotic produced by Streptomyces fradiae. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 138.059
Groups approved
Monoisotopic Weight 138.008195224
Pharmacology
Indication For the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis.
Mechanism of action Fosfomycin is a phosphoenolpyruvate analogue produced by Streptomyces that irreversibly inhibits enolpyruvate transferase (MurA), which prevents the formation of N-acetylmuramic acid, an essential element of the peptidoglycan cell wall.
Absorption Fosfomycin tromethamine is rapidly absorbed following oral administration and converted to fosfomycin. Oral bioavailability under fasting conditions is 37%. When given with food, oral bioavailability is reduced to 30%
Protein binding 0% (not bound to plasma proteins)
Biotransformation No transformation, excreted unchanged
Route of elimination Fosfomycin is excreted unchanged in both urine and feces.
Toxicity LD50>5 g/kg (rats). Side effects may include diarrhea
Affected organisms
  • Enteric bacteria and other eubacteria
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
  • Food decreases Cmax slightly.

Targets


UDP-N-acetylglucosamine 1-carboxyvinyltransferase
Name UDP-N-acetylglucosamine 1-carboxyvinyltransferase
Gene Name murA
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Kim DH, Lees WJ, Kempsell KE, Lane WS, Duncan K, Walsh CT: Characterization of a Cys115 to Asp substitution in the Escherichia coli cell wall biosynthetic enzyme UDP-GlcNAc enolpyruvyl transferase (MurA) that confers resistance to inactivation by the antibiotic fosfomycin. Biochemistry. 1996 Apr 16;35(15):4923-8. - Pubmed
  • Eschenburg S, Priestman M, Schonbrunn E: 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. Epub 2004 Nov 5. - Pubmed
  • McCoy AJ, Sandlin RC, Maurelli AT: 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. - Pubmed
  • Brown ED, Vivas EI, Walsh CT, Kolter R: MurA (MurZ), the enzyme that catalyzes the first committed step in peptidoglycan biosynthesis, is essential in Escherichia coli. J Bacteriol. 1995 Jul;177(14):4194-7. - Pubmed
  • Samland AK, Amrhein N, Macheroux P: 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. - Pubmed
DTHybrid score 2

Predictions


Id Partner name Gene Name Score
2306 UDP-N-acetylglucosamine 1-carboxyvinyltransferase murA 2
2367 UDP-N-acetylglucosamine 1-carboxyvinyltransferase murA 2
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