Department of Biomedical Sciences and Biotechnology, Unit of Biology and Genetics, University of Brescia, Brescia, Italy.
PLoS One. 2012;7(8):e44193. doi: 10.1371/journal.pone.0044193. Epub 2012 Aug 30.
Sialidases are glycohydrolytic enzymes present from virus to mammals that remove sialic acid from oligosaccharide chains. Four different sialidase forms are known in vertebrates: the lysosomal NEU1, the cytosolic NEU2 and the membrane-associated NEU3 and NEU4. These enzymes modulate the cell sialic acid content and are involved in several cellular processes and pathological conditions. Molecular defects in NEU1 are responsible for sialidosis, an inherited disease characterized by lysosomal storage disorder and neurodegeneration. The studies on the biology of sialic acids and sialyltransferases, the anabolic counterparts of sialidases, have revealed a complex picture with more than 50 sialic acid variants selectively present in the different branches of the tree of life. The gain/loss of specific sialoconjugates have been proposed as key events in the evolution of deuterostomes and Homo sapiens, as well as in the host-pathogen interactions. To date, less attention has been paid to the evolution of sialidases. Thus we have conducted a survey on the state of the sialidase family in metazoan. Using an in silico approach, we identified and characterized sialidase orthologs from 21 different organisms distributed among the evolutionary tree: Metazoa relative (Monosiga brevicollis), early Deuterostomia, precursor of Chordata and Vertebrata (teleost fishes, amphibians, reptiles, avians and early and recent mammals). We were able to reconstruct the evolution of the sialidase protein family from the ancestral sialidase NEU1 and identify a new form of the enzyme, NEU5, representing an intermediate step in the evolution leading to the modern NEU3, NEU4 and NEU2. Our study provides new insights on the mechanisms that shaped the substrate specificity and other peculiar properties of the modern mammalian sialidases. Moreover, we further confirm findings on the catalytic residues and identified enzyme loop portions that behave as rapidly diverging regions and may be involved in the evolution of specific properties of sialidases.
唾液酸酶是一种糖水解酶，存在于从病毒到哺乳动物的各种生物中，能够从寡糖链上移除唾液酸。脊椎动物中有四种不同的唾液酸酶形式：溶酶体 NEU1、细胞质 NEU2 和膜相关的 NEU3 和 NEU4。这些酶调节细胞的唾液酸含量，并参与多种细胞过程和病理状况。NEU1 的分子缺陷导致唾液酸贮积症，这是一种遗传性疾病，其特征为溶酶体贮积障碍和神经退行性变。对唾液酸和唾液酸转移酶（唾液酸酶的合成对应物）的生物学研究揭示了一个复杂的图景，其中有超过 50 种唾液酸变体选择性地存在于生命之树的不同分支中。特定唾液酸缀合物的获得/丧失被认为是后口动物和智人以及宿主-病原体相互作用进化的关键事件。迄今为止，人们对唾液酸酶的进化关注较少。因此，我们对后生动物中唾液酸酶家族的进化进行了调查。我们使用一种计算机方法，从进化树中分布的 21 种不同生物中鉴定和描述了唾液酸酶同源物：原生动物（Monosiga brevicollis）、早期后口动物、脊索动物和脊椎动物的前体（硬骨鱼、两栖动物、爬行动物、鸟类和早期和近期的哺乳动物）。我们能够从祖先唾液酸酶 NEU1 重建唾液酸酶蛋白家族的进化，并鉴定出一种新的酶形式 NEU5，它代表了导致现代 NEU3、NEU4 和 NEU2 的进化过程中的一个中间步骤。我们的研究为塑造现代哺乳动物唾液酸酶的底物特异性和其他特殊性质的机制提供了新的见解。此外，我们进一步证实了关于催化残基的发现，并鉴定了酶环部分，这些部分表现为快速分化的区域，可能参与了唾液酸酶特定性质的进化。
