High resolution

Module 2: Figure eNOS activation



Ca2+-dependent activation of endothelial nitric oxide synthase (eNOS).

An important feature of eNOS is its location on the membrane of caveolae (Module 6: Figure caveolae molecular organization). Its membrane localization is facilitated by an N-terminal myristic acid and by two palmitic acid residues attached to two cysteine residues (Cys-15 and Cys-26), whereas its association with the caveolae depends upon its attachment to caveolin, which is responsible for keeping the enzyme inactive under resting conditions. There appears to be a competition between caveolin and calmodulin (CaM) for the caveolin-binding site (amino acids 350–358) on eNOS. In the absence of Ca2+, caveolin dominates, but when Ca2+ increases and binds to CaM, the latter relieves the inhibitory effect of caveolin, and the enzyme is activated to generate NO from arginine using oxygen and NADPH as co-substrates.