Figure 4.

Conformational change in 15LOX-2 induced upon PEBP1 binding allows NO^● binding to the catalytic sites in the presence of SAPE. Panels a and b compare the binding patterns of O₂/NO^● to 15LOX-2 in the presence (a) and absence (b) of complexation with PEBP1. The positions of NO^● (blue dots) and O₂ (red dots) sampled during MD snapshots are displayed. These refer to contacts (within 3.5 Å) between O₂/NO^● and (a) SAPE-bound 15LOX-2/PEBP1 complex and (b) SAPE-bound 15LOX-2 (with O₂/NO^● molecules within 7 Å from any SAPE atom). Both O₂ and NO^● molecules sample the catalytic site in the presence of PEBP1 (panel a, black oval). In the absence of PEBP1 the catalytic site exclusively harbors the O₂ molecules (red oval). Snapshots from another run (Supplementary Figure S5) illustrate the reproducibility of the results. (c) Structural change induced by PEBP1 binding. Structural alignment of 15LOX-2 structure (after 150 ns simulation) in PEBP1-bound (dark grey) and unbound (magenta) forms with SAPE substrate (spheres) and accumulation of NO^● molecules near the loop L172-A179 (orange) on the surface, are shown. Black arrows show the direction of conformational change in the α2 helix and the T166-A179 loop, providing access to both NO^● (blue dots) and O₂ (red dots). Other NO^● molecules attracted by the stearic acid sn-1 chain of SAPE are hidden for better visualization.