FIGURE 7.

A model for 5-LO bound to a phospholipid membrane in the fluid phase, constructed on the basis of homology modeling and data on membrane insertion and angular orientation of 5-LO. The protein structure is modeled using SWISS-MODEL on the basis of rabbit 15-LO crystal structure as a template, and is presented in a ribbon format. The N-terminal β-barrel and the catalytic domains are shown in plum and aqua, respectively. The mesh of gray spheres represents the plane of the phosphate groups of phospholipid molecules. Membrane-interacting and catalytically important residues are shown in the ball-and-stick format and are labeled by blue and red labels, respectively. Tryptophans that insert into the membrane hydrocarbon region are shown in yellow, and those located at the membrane-water interface are shown in orange. Phe¹⁹⁷ and Lys¹⁸³, which interact with the membrane by nonpolar and ionic interactions, are shown in green and purple, respectively. Arg⁴¹¹, which presumably forms an ionic contact with the carboxyl group of arachidonate during the initial step of enzyme-substrate interaction, is shown in magenta. Residues involved in coordination of the iron cofactor are colored according to the atom type. Trp¹³, and partially Trp⁵⁹⁹ and Lys¹⁸³, are underneath the polar groups of lipids and can hardly be seen. His³⁶⁷ is hidden behind the helical ribbon. According to our earlier results (Pande et al., 2004), the symmetry axis of the N-terminal β-barrel domain is tilted at ∼45° with respect to the membrane normal, and the current data suggest that at least one Trp, most likely the Trp⁷⁵, inserts into the membrane as deep as 8–9 Å from the membrane center.