The molecular mechanism of human group IIA phospholipase A2 inactivation by bolinaquinone

✍ Scribed by Maria Chiara Monti; Maria Giovanna Chini; Luigi Margarucci; Alessandra Tosco; Raffaele Riccio; Giuseppe Bifulco; Agostino Casapullo

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 407 KB
• Volume: 22
• Category: Article
• ISSN: 0952-3499
• DOI: 10.1002/jmr.968

✦ Synopsis

Abstract

The molecular basis of the human group IIA secretory phospholipase A~2~ 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, sPLA~2~s 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 Ca^2+^ ion inside the enzyme active site.

The understanding of the sPLA~2~‐IIA inactivation mechanism by BLQ could be useful for the development of a new chemical class of PLA~2~ inhibitors, able to specifically target the enzyme active site. Copyright © 2009 John Wiley & Sons, Ltd.