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 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.

• Authors: Mona D Lee, Christophe Antczak, Yueming Li, Francis M Sirotnak, William G Bornmann, David A Scheinberg
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 312 Issue 2 Pg. 309-15 (Dec 12 2003) ISSN: 0006-291X [Print] United States
• PMID: 14637138 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Enzyme Inhibitors
• Hydroxamic Acids
• Metals
• Amidohydrolases
• peptide deformylase
• actinonin

Topics

• Amidohydrolases (antagonists & inhibitors, biosynthesis, chemistry, pharmacology)
• Burkitt Lymphoma (metabolism)
• Cell Division (drug effects)
• Cloning, Molecular
• Dose-Response Relationship, Drug
• Enzyme Activation
• Enzyme Inhibitors (chemistry)
• Enzyme Stability
• HL-60 Cells (cytology, drug effects)
• Humans
• Hydrogen-Ion Concentration
• Hydroxamic Acids (chemistry)
• Kinetics
• Metals
• Substrate Specificity
• Temperature