Inhibition of Bacterial Peptide Deformylase by Biaryl Acid Analogs
| Autor: | Stephan K. Grant, Barbara G. Green, Jeffrey H. Toney, John W. Kozarich |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Stereochemistry
Biophysics Tetrazoles Aminopeptidases Binding Competitive Biochemistry Amidohydrolases Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound Peptide deformylase Carbonic anhydrase Escherichia coli Tetrazole Carboxylate Enzyme Inhibitors Molecular Biology chemistry.chemical_classification Sulfonamides Methionine biology Biphenyl Compounds Active site Recombinant Proteins Sulfonamide Models Chemical chemistry biology.protein Pharmacophore |
| Zdroj: | Archives of Biochemistry and Biophysics. 375:355-358 |
| ISSN: | 0003-9861 |
| DOI: | 10.1006/abbi.1999.1673 |
| Popis: | Peptide deformylase is an essential eubacterial metalloenzyme involved in the maturation of proteins by cleaving the N-formyl group from N-blocked methionine polypeptides. Biaryl acid analogs containing tetrazole, acyl sulfonamide, or carboxylate pharmacophores were found to be potent inhibitors of recombinant Escherichia coli peptide deformylase. Two of these compounds, a biphenyl tetrazole, compound 1, and a biphenyl acyl sulfonamide, compound 4, were competitive inhibitors with Ki values of 1.2 and 6.0 μM, respectively. By analogy to the binding of related compounds to other metalloenzymes such as Bacteroides fragilis metallo-β-lactamase CcrA and human carbonic anhydrase, a mechanism of inhibition is proposed for these peptide deformylase inhibitors where the acidic moieties form direct ionic interactions with the active site metal cation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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