The molecular mechanism of human group IIA phospholipase A2 inactivation by bolinaquinone.
J Mol Recognit
; 22(6): 530-7, 2009.
Article
em En
| MEDLINE
| ID: mdl-19621421
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sesquiterpenos
/
Fosfolipases A2 do Grupo II
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article