Department of Clinical Science and Translational Medicine, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy.
Department of Experimental Medicine, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy.
Int J Mol Sci. 2024 Feb 13;25(4):2241. doi: 10.3390/ijms25042241.
Lipoxygenases (LOXs) are a family of enzymes that includes different fatty acid oxygenases with a common tridimensional structure. The main functions of LOXs are the production of signaling compounds and the structural modifications of biological membranes. These features of LOXs, their widespread presence in all living organisms, and their involvement in human diseases have attracted the attention of the scientific community over the last decades, leading to several studies mainly focused on understanding their catalytic mechanism and designing effective inhibitors. The aim of this review is to discuss the state-of-the-art of a different, much less explored aspect of LOXs, that is, their interaction with lipid bilayers. To this end, the general architecture of six relevant LOXs (namely human 5-, 12-, and 15-LOX, rabbit 12/15-LOX, coral 8-LOX, and soybean 15-LOX), with different specificity towards the fatty acid substrates, is analyzed through the available crystallographic models. Then, their putative interface with a model membrane is examined in the frame of the conformational flexibility of LOXs, that is due to their peculiar tertiary structure. Finally, the possible future developments that emerge from the available data are discussed.
脂氧合酶（LOXs）是一类酶，包含不同的脂肪酸加氧酶，具有共同的三维结构。LOXs 的主要功能是产生信号化合物和生物膜的结构修饰。这些 LOXs 的特点，它们在所有生物中的广泛存在，以及它们在人类疾病中的参与，引起了科学界过去几十年的关注，导致了许多主要集中在理解其催化机制和设计有效抑制剂的研究。本综述的目的是讨论 LOXs 的一个不同的、研究得较少的方面的最新进展，即它们与脂质双层的相互作用。为此，通过现有的晶体结构模型分析了六种相关 LOXs（即人 5-、12-和 15-LOX、兔 12/15-LOX、珊瑚 8-LOX 和大豆 15-LOX）的一般结构，它们对脂肪酸底物的特异性不同。然后，根据 LOXs 的构象灵活性，即由于其特殊的三级结构，检查其与模型膜的可能界面。最后，讨论了现有数据中出现的可能的未来发展。
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