Gillmor S A, Villaseñor A, Fletterick R, Sigal E, Browner M F
Graduate Group in Biophysics, University of California, San Francisco 94143-0448, USA.
Nat Struct Biol. 1997 Dec;4(12):1003-9. doi: 10.1038/nsb1297-1003.
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 beta-barrel domain. The N-terminal beta-barrel domain has topological and sequence identify 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.
在此，我们报道了哺乳动物15-脂氧合酶的首个结构。该蛋白质由两个结构域组成：一个催化结构域和一个先前未被识别的β-桶状结构域。N端的β-桶状结构域在拓扑结构和序列上与哺乳动物脂肪酶中的一个结构域相同，这表明这些结构域在体内可能具有相似的功能。在C端结构域内，脂氧合酶底物结合位点是一个由结合的抑制剂所界定的疏水口袋。花生四烯酸可以对接至这个深的疏水口袋中，其甲基端向下延伸至口袋底部，而酸端则由酶表面一个保守的碱性残基固定。该结构为哺乳动物脂氧合酶的位置特异性提供了一个统一的假说。
