The structure of mammalian 15-lipoxygenase reveals similarity to the lipases and the determinants of substrate specificity.

摘要: Here we report the first structure of a mammalian 15-lipoxygenase. The protein is composed two domains; catalytic domain and previously unrecognized beta-barrel domain. N-terminal has topological sequence identify to in lipases, suggesting that these domains may have similar functions vivo. Within C-terminal domain, lipoxygenase substrate binding site hydrophobic pocket defined by bound inhibitor. Arachidonic acid can be docked into this deep with methyl end extending down bottom tethered conserved basic residue on surface enzyme. This provides unifying hypothesis for positional specificity lipoxygenases.