6533b821fe1ef96bd127c44b

RESEARCH PRODUCT

PLA2-mediated catalytic activation of its inhibitor 25-acetyl-petrosaspongiolide M: serendipitous identification of a new PLA2 suicide inhibitor.

Raffaele RiccioLuigi Gomez-palomaAgostino CasapulloMaria Chiara Monti

subject

Protein ConformationMarine natural productLigandsBiochemistryMass SpectrometryProtein Structure SecondaryCIRCULAR-DICHROISMchemistry.chemical_compoundProtein structureStructural BiologyBINDINGEnzyme InhibitorsChromatography High Pressure Liquidchemistry.chemical_classificationbiologyMolecular StructureChemistryCircular DichroismHydrolysisTemperatureAcetylationHydrogen-Ion ConcentrationBEE VENOM PHOSPHOLIPASE-A2PoriferaPETROSASPONGIOLIDES M-RBiochemistryCovalent bondINACTIVATIONMANOALIDESpectrometry Mass Electrospray IonizationCYTOSOLIC PHOSPHOLIPASE A(2); BEE VENOM PHOSPHOLIPASE-A2; FLUORESCENCE DISPLACEMENT ASSAY; PETROSASPONGIOLIDES M-R; CIRCULAR-DICHROISM; NATURAL-PRODUCTS; INACTIVATION; MANOALIDE; POTENT; BINDINGStereochemistryBiophysicsGroup II Phospholipases A2CatalysisPhospholipases AAnti-inflammatory compoundManoalidePhospholipase A2NATURAL-PRODUCTSGeneticsTrifluoroacetic acidAnimalsBinding siteOleanolic AcidMolecular BiologyBinding SitesPOTENTCYTOSOLIC PHOSPHOLIPASE A(2)Cell BiologyMolecular WeightKineticsPhospholipases A2EnzymeAcetylationbiology.proteinFLUORESCENCE DISPLACEMENT ASSAYPhospholipase A2 inhibition

description

Abstract25-Acetyl-petrosaspongiolide M (PMAc) (1), a mild non-covalent PLA2 inhibitor, unexpectedly recovers, after incubation with bvPLA2, the ability to covalently modify the enzyme target. This study demonstrates the catalytic effect of bvPLA2 in converting 1 in its deacetylated congener petrosaspongiolide M (PM) (2), a strong covalent PLA2 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.

yearjournalcountryeditionlanguage
2004-11-18FEBS letters
10.1016/j.febslet.2004.10.100https://pubmed.ncbi.nlm.nih.gov/15589831