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

SA Gillmor, A Villaseñor, R Fletterick, E Sigal… - Nature structural …, 1997 - nature.com
SA Gillmor, A Villaseñor, R Fletterick, E Sigal, MF Browner
Nature structural biology, 1997nature.com
Here we report the first structure of a mammalian 15-lipoxygenase. The protein is composed
of two domains; a catalytic domain and a previously unrecognized β-barrel domain. The N-
terminal β-barrel domain has topological and sequence identity to a domain in the
mammalian lipases, suggesting that these domains may have similar functions in vivo.
Within the C-terminal domain, the lipoxygenase substrate binding site is a hydrophobic
pocket defined by a bound inhibitor. Arachidonic acid can be docked into this deep …
Abstract
Here we report the first structure of a mammalian 15-lipoxygenase. The protein is composed of two domains; a catalytic domain and a previously unrecognized β-barrel domain. The N-terminal β-barrel domain has topological and sequence identity to a domain in the mammalian lipases, suggesting that these domains may have similar functions in vivo. Within the C-terminal domain, the lipoxygenase substrate binding site is a hydrophobic pocket defined by a bound inhibitor. Arachidonic acid can be docked into this deep hydrophobic pocket with the methyl end extending down into the bottom of the pocket and the acid end tethered by a conserved basic residue on the surface of the enzyme. This structure provides a unifying hypothesis for the positional specificity of mammalian lipoxygenases.
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