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The molecular mechanism of human group IIA phospholipase A2 inactivation by bolinaquinone
Author(s) -
Monti Maria Chiara,
Chini Maria Giovanna,
Margarucci Luigi,
Tosco Alessandra,
Riccio Raffaele,
Bifulco Giuseppe,
Casapullo Agostino
Publication year - 2009
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.968
Subject(s) - chemistry , phospholipase a2 , active site , phospholipase a , biochemistry , enzyme , stereochemistry , mechanism of action , moiety , phospholipase , in vitro
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.