Citation

Monti MC, Casapullo A, Riccio R, Gomez-Paloma L. FEBS Lett. 2004; 578(3): 269-274.

Copyright

(Copyright © 2004, Federation of European Biochemical Societies, Publisher Elsevier Publishing)

DOI

10.1016/j.febslet.2004.10.100

PMID

15589831

Abstract

25-Acetyl-petrosaspongiolide M (PMAc) (1), a mild non-covalent PLA(2) inhibitor, unexpectedly recovers, after incubation with bvPLA(2), the ability to covalently modify the enzyme target. This study demonstrates the catalytic effect of bvPLA(2) in converting 1 in its deacetylated congener petrosaspongiolide M (PM) (2), a strong covalent PLA(2) inhibitor whose molecular mechanism of inhibition has already been clarified. Moreover, our findings outline the potential role of PMAc as anti-inflammatory pro-drug, by virtue of its ability of delivering the active PM agent at the site of inflammation, functioning as a suicide inhibitor.

Language: en

Keywords

Acetylation; Animals; Binding Sites; Catalysis; Chromatography, High Pressure Liquid; Circular Dichroism; Enzyme Inhibitors; Group II Phospholipases A2; Hydrogen-Ion Concentration; Hydrolysis; Kinetics; Ligands; Mass Spectrometry; Molecular Structure; Molecular Weight; Oleanolic Acid; Phospholipases A; Phospholipases A2; Porifera; Protein Conformation; Protein Structure, Secondary; Spectrometry, Mass, Electrospray Ionization; Temperature