The molecular basis of the human group IIA secretory phospholipase A2 inactivation by bolinaquinone (BLQ), a hydroxyquinone marine terpenoid, has been investigated for the comprehension of its relevant antiinflammatory properties, through the combination of spectroscopic techniques, biosensors analysis, mass spectrometry (MS) and molecular docking. Indeed, sPLA2s are well known to be implicated in the pathogenesis of inflammation such as rheumatoid arthritis, septic shock, psoriasis and asthma. Our results suggest a mechanism of competitive inhibition guided by a non-covalent molecular recognition event, disclosing the key role of the BLQ hydroxyl-quinone moiety in the chelation of the catalytic Ca2R ion inside the enzyme active site. The understanding of the sPLA2-IIA inactivation mechanism by BLQ could be useful for the development of a new chemical class of PLA2 inhibitors, able to specifically target the enzyme active site.
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