IgG Endopeptidase SeMac does not Inhibit Opsonophagocytosis of Streptococcus equi Subspecies equi by Horse Polymorphonuclear Leukocytes.
IgG Endopeptidase SeMac does not Inhibit Opsonophagocytosis of Streptococcus equi Subspecies equi by Horse Polymorphonuclear Leukocytes.
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DOI：
10.2174/1874285801004010020
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发表时间：
2010-04-08
期刊：
影响因子：
--
通讯作者：
Lei B
中科院分区：
文献类型：
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作者：
Liu M;Lei B
由A组链球菌（GAS）分泌的Mac蛋白抑制人多形核白细胞（PMN）对GAS的调理吞噬作用。该蛋白还具有针对人免疫球蛋白G（IgG）的内肽酶活性，并且Cys94、His262和Asp284对于酶活性是关键的。马病原体马链球菌马亚种产生Mac的同源物（SeMac）。对SeMac进行表征以确定SeMac是否具有IgG内肽酶活性并抑制S.马PMNs将该基因克隆，并在大肠杆菌中过表达重组SeMac并纯化至均一。实验性S.马感染和马的S.马血清转化为SeMac，表明SeMac在感染期间体内产生。SeMac具有抗人IgG的内肽酶活性。然而，该蛋白质仅切割马IgG的一小部分，其可能仅为IgG1。将Cys102替换为Ser或将His272替换为Ala会使SeMac的酶活性丧失，并且Asp294Ala突变会大大降低酶活性。SeMac不抑制S.马的中性粒细胞对GAS的调理吞噬作用，而人的中性粒细胞对GAS的调理吞噬作用。因此，SeMac是一种半胱氨酸内肽酶，对马IgG的活性有限，必须具有其他功能。
The secreted Mac protein made by group A Streptococcus (GAS) inhibits opsonophagocytosis of GAS by human polymorphonuclear leukocytes (PMNs). This protein also has the endopeptidase activity against human immunoglobulin G (IgG), and the Cys94, His262 and Asp284 are critical for the enzymatic activity. The horse pathogen Streptococcus equi subspecies equi produces a homologue of Mac (SeMac). SeMac was characterized to determine whether SeMac has IgG endopeptidase activity and inhibits opsonophagocytosis of S. equi by horse PMNs. The gene was cloned and recombinant SeMac was overexpressed in Escherichia coli and purified to homogeneity. Mice with experimental S. equi infection and horses with strangles caused by S. equi seroconverted to SeMac, indicating that SeMac is produced in vivo during infection. SeMac has endopeptidase activity against human IgG. However, the protein just cleaves a small fraction, which may be IgG1 only, of horse IgG. Replacement of Cys102 with Ser or His272 with Ala abolishes the enzymatic activity of SeMac, and the Asp294Ala mutation greatly decreases the enzymatic activity. SeMac does not inhibit opsonophagocytosis of S. equi by horse PMNs but opsonophagocytosis of GAS by human PMNs. Thus, SeMac is a cysteine endopeptidase with a limited activity against horse IgG and must have other function.