Thermodynamic properties of leukotriene A 4 hydrolase inhibitors.

The leukotriene A ₄ hydrolase (LTA ₄ H) is a bifunctional enzyme, containing a peptidase and a hydrolase activity both activities having opposing functions regulating inflammatory response. The hydrolase activity is responsible for the conversion of leukotriene A ₄ to pro-inflammatory leukotriene B ₄ , and hence, selective inhibitors of the hydrolase activity are of high pharmacological interest. Here we present the thermodynamic characterization of structurally distinct inhibitors of the LTA ₄ H that occupy different regions of the binding site using different biophysical methods. An in silico method for the determination of stabilized water molecules in the binding site of the apo structure of LTA ₄ H is used to interpret the measured thermodynamic data and provided insights for design of novel LTA ₄ H inhibitors.
(Copyright © 2016. Published by Elsevier Ltd.)