The peroxidase-cyclooxygenase superfamily:: reconstructed evolution of critical enzymes of the innate immune system
The peroxidase-cyclooxygenase superfamily:: reconstructed evolution of critical enzymes of the innate immune system
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DOI：
10.1002/prot.21950
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发表时间：
2008-08-01
影响因子：
2.9
通讯作者：
Obinger, Christian
中科院分区：
文献类型：
--
作者：
Zamocky, Marcel;Jakopitsch, Christa;Obinger, Christian
作者重建了哺乳动物含血红素过氧化物酶主要进化线的系统发育关系。深入研究的人髓过氧化物酶，嗜酸性粒细胞过氧化物酶，和乳过氧化物酶，参与宿主防御感染的序列，对齐与新发现的开放阅读框架编码高度相似的推定过氧化物酶结构域在所有的生命王国。使用邻居连接、最大简约和最大似然方法重建进化关系。结果表明，该酶超家族遵循多基因家族演化的生灭模型，包含多种功能的蛋白质，可分为7个亚家族。基于发生和两种主要酶活性与这些金属蛋白相关的事实，他们提出了这个广泛分布的含血红素的氧化还原酶组的名称过氧化物酶-环氧合酶超家族。众所周知的哺乳动物过氧化物酶的结构-功能关系形成了所有亚家族的关键检查的基础。所提出的数据明确表明，哺乳动物血红素过氧化物酶的前身基因在进化的早期已经分离。在生物体产生获得性免疫之前，它们的抗微生物防御依赖于病原体入侵时招募的酶，这些酶可以产生抗微生物反应产物。因此，这些过氧化物血红素蛋白进化为先天免疫防御系统的重要组成部分。这项工作表明，即使在某些原核生物中，也发现编码推定的抗菌酶的基因为一组细菌提供了优于其他细菌的进化优势。
The authors have reconstructed the phylogenetic relationships of the main evolutionary lines of mammalian heme containing peroxidases. The sequences of intensively investigated human myeloperoxidase, eosinophil peroxidase, and lactoperoxidase, which participate in host defence against infections, were aligned together with newly found open reading frames coding for highly similar putative peroxidase domains in all kingdoms of life. The evolutionary relationships were reconstructed using neighbor-joining, maximum parsimony, and maximum likelihood methods. It is demonstrated that this enzyme superfamily obeys the rules of birth-and-death model of multigene family evolution and contains proteins with a variety of function that could be grouped in seven subfamilies. On the basis of occurrence and the fact that two main enzymatic activities are related with these metalloproteins, they propose the name peroxidase-cyclooxygenase superfamily for this widely spread group of heme-containing oxidoreductases. Well known structure-function relationships in mammalian peroxidases formed the basis for the critical inspection of all subfamilies. The presented data unequivocally suggest that predecessor genes of mammalian heme peroxidases have segregated very early in evolution. Before organisms developed an acquired immunity, their antimicrobial defence depended on enzymes that were recruited upon pathogen invasion and could produce antimicrobial reaction products. Thus, these peroxidatic heme proteins evolved to important components in the innate immune defence system. This work shows that even in certain prokaryotic organisms, genes encoding putative antimicrobial enzymes are found providing a group of bacteria with an evolutionary advantage over the others.