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哺乳动物 ALOX 同工酶的结构和功能生物学，特别强调酶二聚化及其变构特性。

Structural and Functional Biology of Mammalian ALOX Isoforms with Particular Emphasis on Enzyme Dimerization and Their Allosteric Properties.

机构信息

Lomonosov Institute of Fine Chemical Technologies, MIREA-Russian Technological University, Vernadskogo pr. 86, Moscow 119571, Russia.

Department of Biochemistry, Charite, University Medicine Berlin, Corporate Member of Free University Berlin, Humboldt University Berlin and Berlin Institute of Health, Charitéplatz 1, D-10117 Berlin, Germany.

出版信息

Int J Mol Sci. 2024 Nov 9;25(22):12058. doi: 10.3390/ijms252212058.

DOI:10.3390/ijms252212058
PMID:39596127
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11593649/
Abstract

The human genome involves six functional arachidonic acid (AA) lipoxygenase () genes, and the corresponding enzymes (ALOX15, ALOX15B, ALOX12, ALOX12B, ALOXE3, ALOX5) have been implicated in cell differentiations and in the pathogenesis of inflammatory, hyperproliferative, metabolic, and neurological disorders. Humans express two different AA 15-lipoxygenating ALOX isoforms, and these enzymes are called ALOX15 (15-LOX1) and ALOX15B (15-LOX2). Chromosomal localization, sequence alignments, and comparison of the enzyme properties suggest that pig and mouse ALOX15 orthologs (leukocyte-type 12-LOX) on the one hand and rabbit and human ALOX15 orthologs on the other (reticulocyte-type 15-LOX1) belong to the same enzyme family despite their different reaction specificities with AA as a substrate. In contrast, human ALOX12 (platelet-type 12-LOX), as well as pig and mouse ALOX15 (leukocyte-type 12-LOX), belong to different enzyme families, although they exhibit a similar reaction specificity with AA as a substrate. The complex multiplicity of mammalian ALOX isoforms and the controversial enzyme nomenclatures are highly confusing and prompted us to summarize the current knowledge on the biological functions, enzymatic properties, and allosteric regulation mechanisms of mammalian ALOX15, ALOX15B, and ALOX12 orthologs that belong to three different enzyme sub-families.

摘要

人类基因组涉及六个功能性花生四烯酸（AA）脂氧合酶（）基因，相应的酶（ALOX15、ALOX15B、ALOX12、ALOX12B、ALOXE3、ALOX5）已被牵连到细胞分化和炎症、过度增殖、代谢和神经紊乱的发病机制中。人类表达两种不同的 AA 15-脂氧合酶 ALOX 同工型，这些酶分别称为 ALOX15（15-LOX1）和 ALOX15B（15-LOX2）。染色体定位、序列比对和酶特性比较表明，猪和鼠的 ALOX15 同源物（白细胞型 12-LOX）与兔和人的 ALOX15 同源物（网织红细胞型 15-LOX1）属于同一酶家族，尽管它们作为底物的 AA 反应特异性不同。相比之下，人类 ALOX12（血小板型 12-LOX）以及猪和鼠的 ALOX15（白细胞型 12-LOX）属于不同的酶家族，尽管它们作为底物的 AA 反应特异性相似。哺乳动物 ALOX 同工型的复杂多样性和有争议的酶命名法令人非常困惑，促使我们总结了目前关于属于三个不同酶亚家族的哺乳动物 ALOX15、ALOX15B 和 ALOX12 同源物的生物学功能、酶特性和变构调节机制的知识。

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