A new human peptide deformylase inhibitable by actinonin Journal Article
| Authors: | Lee, M. D.; Antczak, C.; Li, Y.; Sirotnak, F. M.; Bornmann, W. G.; Scheinberg, D. A. |
| Article Title: | A new human peptide deformylase inhibitable by actinonin |
| Abstract: | 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°C, and in a low KCl ionic strength buffer. Actinonin inhibits HsPDF activity with an IC50 of 43nM and kills Daudi and HL60 human cancer cell lines with an LC50 of 5.3 and 8.8μM, respectively. The inhibition of HsPDF may provide an explanation for the mechanism by which actinonin is cytotoxic against various human tumor cell lines. © 2003 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; protein expression; human cell; comparative study; cell division; enzyme inhibition; ph; cytotoxicity; enzyme activation; dose-response relationship, drug; enzyme activity; bacteria (microorganisms); cloning, molecular; bacterial protein; kinetics; enzyme inhibitors; substrate specificity; hydroxamic acids; temperature; catalysis; enzyme kinetics; cobalt; zinc; ic 50; peptide deformylase; actinonin; amidohydrolases; nickel; burkitt lymphoma; hydrogen-ion concentration; metals; enzyme stability; vegetable protein; peptide deformylase inhibitor; potassium chloride; human peptide deformylase; buffer; hl-60 cells; cell strain hl 60; humans; human; priority journal; article; daudi cell; formyl peptides; lc 50 |
| Journal Title: | Biochemical and Biophysical Research Communications |
| Volume: | 312 |
| Issue: | 2 |
| ISSN: | 0006-291X |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2003-12-12 |
| Start Page: | 309 |
| End Page: | 315 |
| Language: | English |
| DOI: | 10.1016/j.bbrc.2003.10.123 |
| PUBMED: | 14637138 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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112Bornmann -
499Scheinberg -
40Antczak -
132Li -
184Sirotnak
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