Orthologues of Streptococcus pyogenes nuclease A (SpnA) and Streptococcal 5′-nucleotidase A (S5nA) found in Streptococcus iniae

Orthologues of Streptococcus pyogenes nuclease A (SpnA) and Streptococcal 5′-nucleotidase A (S5nA) found in Streptococcus iniae
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DOI:
10.1093/jb/mvy039
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发表时间:
2018-08
期刊:
The Journal of Biochemistry
影响因子:
--
通讯作者:
Kar Yan Soh;J. Loh;T. Proft
Kar Yan Soh;J. Loh;T. Proft
中科院分区:
其他
文献类型:
--
作者:
Kar Yan Soh;J. Loh;T. Proft

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化脓性链球菌核酸酶A(SpnA)和链球菌5'核苷酶A(S5 nA)是近年来发现的两种人类致病链球菌的毒力因子。化脓体外研究表明,SpnA是一种切割ssDNA和dsDNA的核酸酶,包括中性粒细胞胞外陷阱的DNA骨架。S5 nA被证明水解AMP和ADP,但不水解ATP,以产生免疫调节分子腺苷。S5 nA还从dAMP产生巨噬细胞毒性脱氧腺苷。然而,这两种酶的详细体内研究受到了使用目前这种独特的人类病原体动物模型的困难的阻碍。在这里,我们报告了两个新的酶从鱼类病原体海豚链球菌,显示相似的SpnA和S5 nA的氨基酸序列,蛋白质结构域结构和生化特性的鉴定。我们认为SpnAi和S5 nAi是S.化脓性链球菌的酶,提供了一个基本原理,分析在体内功能的两种酶使用的S。iniae-斑马鱼感染模型。
Streptococcus pyogenes nuclease A (SpnA) and streptococcal 5' nucleosidase A (S5nA) are two recently described virulence factors from the human pathogen S. pyogenes. In vitro studies have shown that SpnA is a nuclease that cleaves ssDNA and dsDNA, including the DNA backbone of neutrophil extracellular traps. S5nA was shown to hydrolyse AMP and ADP, but not ATP, to generate the immunomodulatory molecule adenosine. S5nA also generates the macrophage-toxic deoxyadenosine from dAMP. However, detailed in vivo studies of the two enzymes have been hampered by difficulties with using current animal models for this exclusive human pathogen. Here we report the identification of two novel enzymes from the fish pathogen Streptococcus iniae that show similarities to SpnA and S5nA in amino acid sequence, protein domain structure and biochemical properties. We propose that SpnAi and S5nAi are orthologues of the S. pyogenes enzymes, providing a rationale to analyse the in vivo function of the two enzymes using a S. iniae-zebrafish infection model.