STRUCTURAL REQUIREMENTS FOR THE BINDING OF FATTY-ACIDS TO 5-LIPOXYGENASE-ACTIVATING PROTEIN

5-Lipoxygenase-activating protein is required for cellular leukotriene synthesis and is the target of the leukotriene biosynthesis inhibitor s MK-886 ert-butylthio-1H-indol-2-yl]-2,2-dimethylpropanoic acid) and MK-591 lin-2-ylmethoxy)-indol-2-yl]-2,2-dimethylpropanoic acid). Recen t studies demonstrate that 5-lipoxygenase-activating protein binds ara chidonic acid and stimulates the utilization of this substrate by 5-li poxygenase. The present study utilizes a radioligand binding assay to assess the affinity of 5-lipoxygenase-activating protein for arachidon ic acid and the specificity of the fatty acid binding site on 5-lipoxy genase-activating protein. Our findings demonstrate that the presence of a free carboxyl group on fatty acids or leukotriene biosynthesis in hibitors which interact with 5-lipoxygenase-activating protein is not required for specific binding to the protein. However, the degree of s aturation significantly affects the affinity of fatty acids for 5-lipo xygenase-activating protein.