Molecular modeling of the additional inhibitor site located in secretory phospholipase A(2)

Journal of Biomolecular Structure & Dynamics
Gurusamy OmprabaZiauddin Ahamed Rafi

Abstract

Phospholipase A(2) belongs to a super family of enzymes that is massively over expressed in a variety of severe inflammatory diseases, which degrades membrane phospholipids. It has also been reported that this activity leads to loss of tissue, organ integrity and function. This enzyme is an important target for anti-inflammatory drugs. Unsaturated aldehyde terpenoids (non-specific inhibitors) are also being reported, however, they are known to irreversibly modify the enzyme and its action through covalent bond formation. Conformational analysis of secretory phospholipase A(2) indicates that the enzyme's known active site (hydrophobic site) is highly flexible. The studies revealed an additional inhibitor interaction site at the interfacial allosteric binding region of the enzyme. This study unequivocally establishes that non-specific inhibitors like aldehyde terpenoids can simultaneously interact with the enzyme at dual active sites and hence they are reported to be very effective for their inhibitory action.

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Citations

Jun 24, 2011·Journal of Biomolecular Structure & Dynamics·Deok-Soo KimJong Bhak
Jun 15, 2012·Journal of Biomolecular Structure & Dynamics·Weng Ieong Tou, Calvin Yu-Chian Chen
Jun 13, 2012·Journal of Biomolecular Structure & Dynamics·Mahdi AlijanianzadehAli Akbar Moosavi-Movahedi
Jun 27, 2012·Journal of Biomolecular Structure & Dynamics·Guojun ShiSichuan Xu
Jun 24, 2011·Journal of Biomolecular Structure & Dynamics·Huan-Zhang XieSheng-Yong Yang
Apr 8, 2011·Journal of Biomolecular Structure & Dynamics·Teodorico C RamalhoElaine F F da Cunha
Apr 8, 2011·Journal of Biomolecular Structure & Dynamics·Maliheh S AtriAmir Niasari-Naslaji
Aug 31, 2011·Journal of Biomolecular Structure & Dynamics·Ping LiCun Xin Wang
Jun 24, 2011·Journal of Biomolecular Structure & Dynamics·Jayson F Varguhese, Yumin Li
Jun 24, 2011·Journal of Biomolecular Structure & Dynamics·Wilian A CortopassiTanos C C França
Aug 31, 2011·Journal of Biomolecular Structure & Dynamics·Adeleh DivsalarRamaswamy H Sarma

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