The anti-angiogenic agent fumagillin covalently modifies a conserved active-site histidine in the Escherichia coli methionine aminopeptidase
| Autor: | Allen M. Orville, W.T. Lowther, McMillen Da, Brian W. Matthews |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Methionyl aminopeptidase
Biology medicine.disease_cause Aminopeptidases Mass Spectrometry chemistry.chemical_compound Cyclohexanes Escherichia coli medicine Methionyl Aminopeptidases Histidine Fumagillin Binding site DNA Primers Binding Sites Multidisciplinary Methionine Base Sequence Neovascularization Pathologic Active site Biological Sciences Recombinant Proteins METAP2 chemistry Biochemistry Fatty Acids Unsaturated biology.protein Sesquiterpenes Protein Binding medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 95:12153-12157 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.95.21.12153 |
| Popis: | Methionine aminopeptidase (MetAP) exists in two forms (type I and type II), both of which remove the N-terminal methionine from proteins. It previously has been shown that the type II enzyme is the molecular target of fumagillin and ovalicin, two epoxide-containing natural products that inhibit angiogenesis and suppress tumor growth. By using mass spectrometry, N-terminal sequence analysis, and electronic absorption spectroscopy we show that fumagillin and ovalicin covalently modify a conserved histidine residue in the active site of the MetAP from Escherichia coli , a type I enzyme. Because all of the key active site residues are conserved, it is likely that a similar modification occurs in the type II enzymes. This modification, by occluding the active site, may prevent the action of MetAP on proteins or peptides involved in angiogenesis. In addition, the results suggest that these compounds may be effective pharmacological agents against pathogenic and resistant forms of E. coli and other microorganisms. |
| Databáze: | OpenAIRE |
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