Institute of Biochemistry, University Medicine Berlin - Charité, Germany.
Arch Biochem Biophys. 2010 Nov 15;503(2):161-74. doi: 10.1016/j.abb.2010.08.016. Epub 2010 Aug 27.
Lipoxygenases (LOXs) are lipid peroxidizing enzymes, implicated in the pathogenesis of inflammatory and hyperproliferative diseases, which represent potential targets for pharmacological intervention. Although soybean LOX1 was discovered more than 60years ago, the structural biology of these enzymes was not studied until the mid 1990s. In 1993 the first crystal structure for a plant LOX was solved and following this protein biochemistry and molecular enzymology became major fields in LOX research. This review focuses on recent developments in molecular enzymology of LOXs and summarizes our current understanding of the structural basis of LOX catalysis. Various hypotheses explaining the reaction specificity of different isoforms are critically reviewed and their pros and cons briefly discussed. Moreover, we summarize the current knowledge of LOX evolution by profiling the existence of LOX-related genomic sequences in the three kingdoms of life. Such sequences are found in eukaryotes and bacteria but not in archaea. Although the biological role of LOXs in lower organisms is far from clear, sequence data suggests that this enzyme family might have evolved shortly after the appearance of atmospheric oxygen on earth.
脂氧合酶（LOXs）是脂质过氧化酶，参与炎症和过度增殖性疾病的发病机制，是药物干预的潜在靶点。尽管大豆 LOX1 早在 60 多年前就被发现，但直到 20 世纪 90 年代中期，这些酶的结构生物学才得到研究。1993 年，首次解析了一种植物 LOX 的晶体结构，此后，蛋白质生物化学和分子酶学成为 LOX 研究的主要领域。本综述重点介绍了 LOX 分子酶学的最新进展，并总结了我们目前对 LOX 催化结构基础的理解。对不同同工酶的反应特异性的各种假设进行了批判性的回顾，并简要讨论了它们的优缺点。此外，我们通过分析生命三界中与 LOX 相关的基因组序列的存在，总结了 LOX 进化的现有知识。这样的序列存在于真核生物和细菌中，但不存在于古菌中。尽管 LOX 在低等生物中的生物学作用还远不清楚，但序列数据表明，这种酶家族可能是在地球大气中出现氧气后不久进化而来的。
