Molecules, Vol. 25, Pages 4459: Structural and Functional Aspects of Targeting the Secreted Human Group IIA Phospholipase A2

Molecules, Vol. 25, Pages 4459: Structural and Functional Aspects of Targeting the Secreted Human Group IIA Phospholipase A2 Molecules doi: 10.3390/molecules25194459 Authors: Kim Chen Mann Bastard F. Scott Church Human group IIA secretory phospholipase A2 (hGIIA) promotes the proliferation of cancer cells, making it a compelling therapeutic target, but it is also significant in other inflammatory conditions. Consequently, suitable inhibitors of hGIIA have always been sought. The activation of phospholipases A2 and the catalysis of glycerophospholipid substrates generally leads to the release of fatty acids such as arachidonic acid (AA) and lysophospholipid, which are then converted to mediator compounds, including prostaglandins, leukotrienes, and the platelet-activating factor. However, this ability of hGIIA to provide AA is not a complete explanation of its biological role in inflammation, as it has now been shown that it also exerts proinflammatory effects by a catalysis-independent mechanism. This mechanism is likely to be highly dependent on key specific molecular interactions, and the full mechanistic descriptions of this remain elusive. The current candidates for the protein partners that may mediate this catalysis-independent mechanism are also introduced in this review. A key discovery has been that selective inhibition of the catalysis-independent activity of hGIIA is achieved with cyclised derivatives of a pentapeptide, FLSYK, derived from ...
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research