Inherited human cPLA_2α deficiency is associated with impaired eicosanoid biosynthesis, small intestinal ulceration, and platelet dysfunction
J. Clin. Invest. David H. Adler, et al. 118:2121 doi:10.1172/JCI30473 [Go to this article.]

Figure 8
cPLA_2α tertiary structure and location of amino acid substitutions. The cPLA_2α structure is depicted as a ribbon diagram with α-helices in red, β-strands as blue arrows, loops in gray, and Ca²⁺ ions as yellow spheres (center). The locations of described amino acid side-chain substitutions are highlighted in green. Three magnified views highlight each mutation. In the left panel, the Ca²⁺ binding domain is highlighted and shows the S111 position. The upper panel shows that the catalytic domain contains an active site composed of the catalytic dyad of Ser228 and Asp549. Arg200 is also required for catalytic activity (functionally obligate amino acids are shown with yellow carbon atoms and bonds) (11). Arg485 is in proximity to a cluster of lysine residues (blue) that are essential for interfacial binding of cPLA_2α (12) and for binding PIP₂ (13). p.[R485] is located in a cleft in a helical region containing several positively charged residues in the membrane-facing region of the catalytic domain (11), where the side-chain guanido group forms 2 stabilizing hydrogen-bonding interactions within this fold. A “hinged lid,” which prevents exposure of the active site to substrate until interaction with a lipid membrane is shown in purple. The right panel depicts the location of Lys651, the relative position of which has not been determined.