DT-Web

DB00626 - Bacitracin


Identification
Name Bacitracin
Accession Number DB00626 (APRD00816)
Type small molecule
Description Bacitracin is a mixture of related cyclic polypeptides produced by organisms of the licheniformis group of Bacillus subtilis var Tracy. Its unique name derives from the fact that the bacillus producing it was first isolated in 1943 from a knee scrape from a girl named Margaret Tracy. As a toxic and difficult-to-use antibiotic, bacitracin doesn't work well orally. However, it is very effective topically. Bacitracin is synthesised via the so-called nonribosomal peptide synthetases (NRPSs), which means that ribosomes are not involved in its synthesis.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 1422.693
Groups approved
Monoisotopic Weight 1421.748941023
Pharmacology
Indication For the treatment of infants with pneumonia and empyema caused by staphylococci shown to be susceptible to the drug. Also used in ointment form for topical treatment of a variety of localized skin and eye infections, as well as for the prevention of wound infections. Used against gram positive bacteria. Bacitracin is also used as an inhibitor of proteases and other enzymes. However, specific activity of bactracin's inhibition of protein disulfide isomerase has been called into question.
Mechanism of action Bacitracin intereferes with the dephosphorylation of the 55-carbon, biphosphate lipid transport molecule C55-isoprenyl pyrophosphate (undecaprenyl pyrophosphate), which carries the building blocks of the peptidoglycan bacterial cell wall outside the inner membrane for construction. Bacitracin binds divalent transition metal ions (Mn(II), Co(II), Ni(II), Cu(II), and Zn(II)) which binds and oxidatively cleave DNA.
Absorption Absorption of bacitracin following intramuscular injection is rapid and complete. Absorption from the gastrointestinal tract following oral administration is not appreciable. Absorption following topical application is negligible.
Protein binding Not Available
Biotransformation Not Available
Route of elimination The drug is excreted slowly by glomerular filtration.
Toxicity Oral, mouse: LD50 = >3750 mg/kg.
Affected organisms
  • Enteric bacteria and other eubacteria
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


C55-isoprenyl pyrophosphate
Name C55-isoprenyl pyrophosphate
Gene Name Not Available
Pharmacological action yes
Actions antagonist
References
  • Stone KJ, Strominger JL: Mechanism of action of bacitracin: complexation with metal ion and C 55 -isoprenyl pyrophosphate. Proc Natl Acad Sci U S A. 1971 Dec;68(12):3223-7. - Pubmed
DTHybrid score Not Available
Insulin-degrading enzyme
Name Insulin-degrading enzyme
Gene Name IDE
Pharmacological action yes
Actions inhibitor
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Medina V, Kesner L, Stracher A: Purification of nonantibiotic insulinase inhibitors from bacitracin. Biochem Med Metab Biol. 1993 Apr;49(2):255-64. - Pubmed
DTHybrid score 0.7157
Alpha-2-macroglobulin
Name Alpha-2-macroglobulin
Gene Name A2M
Pharmacological action unknown
Actions inhibitor
References
  • Maxfield FR, Davies PJ, Klempner L, Willingham MC, Pastan I: Epidermal growth factor stimulation of DNA synthesis is potentiated by compounds that inhibit its clustering in coated pits. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5731-5. - Pubmed
  • Dickson RB, Willingham MC, Pastan I: Binding and internalization of 125I-alpha 2-macroglobulin by cultured fibroblasts. J Biol Chem. 1981 Apr 10;256(7):3454-9. - Pubmed
  • Dickson RB, Willingham MC, Gallo M, Pastan I: Inhibition by bacitracin of high affinity binding of 125I-alpha 2M to plasma membranes. FEBS Lett. 1981 Apr 20;126(2):265-8. - Pubmed
  • Hanover JA, Cheng S, Willingham MC, Pastan IH: alpha 2-Macroglobulin binding to cultured fibroblasts. Solubilization and partial purification of binding sites. J Biol Chem. 1983 Jan 10;258(1):370-7. - Pubmed
  • Gliemann J, Larsen TR, Sottrup-Jensen L: Cell association and degradation of alpha 2-macroglobulin-trypsin complexes in hepatocytes and adipocytes. Biochim Biophys Acta. 1983 Mar 31;756(2):230-7. - Pubmed
DTHybrid score 1.0613

Predictions


Id Partner name Gene Name Score
1952 Alpha-2-antiplasmin SERPINF2 0.2355
2146 Fibronectin FN1 0.2354
950 Alpha platelet-derived growth factor receptor PDGFRA 0.1465
228 Beta platelet-derived growth factor receptor PDGFRB 0.1415
3849 Insulin-like growth factor-binding protein 7 IGFBP7 0.0913
2009 Protein NOV homolog NOV 0.0913
1949 Carboxypeptidase E CPE 0.0913
3847 Neuroendocrine convertase 2 PCSK2 0.0912
3850 Synaptotagmin-like protein 4 SYTL4 0.0912
3848 Neuroendocrine convertase 1 PCSK1 0.0912
3846 Retinoblastoma-associated protein RB1 0.0912
1244 Low-density lipoprotein receptor-related protein 2 LRP2 0.0767
958 Insulin-like growth factor 1 receptor IGF1R 0.0646
1243 Cathepsin D CTSD 0.0634
36 Insulin receptor INSR 0.0633
3844 HLA class II histocompatibility antigen, DQ(6) alpha chain HLA-DQA2 0.0505
4200 Cytochrome P450 1A2 CYP1A2 0.0304
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