A new human peptide deformylase inhibitable by actinonin
| Autor: | Francis M. Sirotnak, David A. Scheinberg, Christophe Antczak, William Bornmann, Mona D Lee, Yue-Ming Li |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Biophysics
Peptide HL-60 Cells Hydroxamic Acids Biochemistry Amidohydrolases Substrate Specificity Peptide deformylase chemistry.chemical_compound Enzyme activator Enzyme Stability Humans Enzyme kinetics Cloning Molecular Enzyme Inhibitors Actinonin Molecular Biology IC50 chemistry.chemical_classification Dose-Response Relationship Drug Temperature Cell Biology Hydrogen-Ion Concentration Burkitt Lymphoma Enzyme Activation Kinetics Enzyme chemistry Cell culture Metals Cell Division |
| Zdroj: | Biochemical and biophysical research communications. 312(2) |
| ISSN: | 0006-291X |
| Popis: | Peptide deformylases (PDFs) have been investigated as potential specific targets for antibiotics, but the possible existence of a functional human PDF (HsPDF) presents a potential hurdle to the design of specific drugs. We have expression cloned a HsPDF that has deformylase activity, although it is a slower and catalytically less active enzyme than bacterial or plant PDFs. A cobalt-substituted form of HsPDF (but not nickel or zinc) is active, and the enzyme appears to be active at a pH between 6.0 and 7.2, a temperature range of 25-50 degrees C, and in a low KCl ionic strength buffer. Actinonin inhibits HsPDF activity with an IC50 of 43 nM and kills Daudi and HL60 human cancer cell lines with an LC50 of 5.3 and 8.8 microM, respectively. The inhibition of HsPDF may provide an explanation for the mechanism by which actinonin is cytotoxic against various human tumor cell lines. |
| Databáze: | OpenAIRE |
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