论文代写:ATX蛋白的组成

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03/04/2018

论文代写:ATX蛋白的组成

ATX蛋白由4个结构域组成,其中包括2个N​​末端生长调节素-B(SMB)结构域。其次是催化结构域(PDE)和C-末端核酸酶样结构域(NUC)(15)。 SMB域在蛋白质 – 蛋白质相互作用中起着不可或缺的作用ATX的晶体结构表明SMB结构域在一侧与催化PDE结构域相互作用。发现它们与其结构另一侧的NUC域相互作用。 PDE结构域与原型NPP结构相似。该化合物从Xanthomonasaxonopodis获得。与序列比较的预测具有相似性。已经观察到该结构是碱性磷酸酶的进化相对物。发现ATX是大约15的深疏水性脂质结合口袋。有单人住房。尽管如此,二酰基磷脂不适应。观察到LPA(14:0)的最佳深度(16)。随后的研究表明,脂质结合口袋是常年“开放”的。这表明LPC底物可以永久性地进入活性部位。

论文代写:ATX蛋白的组成
这将通过“底物去稳定化”驱动催化作用,其中降低了磷酸二酯水解反应的活化能垒(16)。发现ATX水解溶血磷脂的头部基团。观察到溶血磷脂酸(1-或2-酰基-sn-甘油-3-磷酸,LPA)与鞘氨醇磷酸胆碱起作用并产生鞘氨醇1-磷酸(S1P)(17)。在结构的另一侧,LPA和S1P是ATX的强抑制剂。它们对酶有亲和力。比通常的TX基板高出1000倍(18)。 ATX被称为血液LPA的主要来源,然而,不适用于S1P(19,20)。 ATX在人类的许多器官中表达,其最高mRNA水平在脑,卵巢,神经系统,消化器皿和肾脏中检测到。在淋巴结中发现相对较高的ATX mRNA水平。具体而言,它处于高浓度的内皮细胞。内皮细胞是进入淋巴细胞进入的重要控制因素(21,22)。

论文代写:ATX蛋白的组成

ATX protein consists of 4 domains, which include 2 N-terminal somatomedin-B (SMB) domains. It is followed by catalytic domain (PDE) and C-terminus nuclease-like domain (NUC) (15). SMB domains play an integral role in protein–protein interactions. The crystal structure of ATX indicatesSMB domains interact with catalytic PDE domain on one side. They are found to interact with NUC domain on the other side of its structure. The structure of PDE domain is similar to that of the prototypic NPP. The compound is obtained from Xanthomonasaxonopodis. There is similarity to the prediction from sequence comparisons. It has been observed that the structure is an evolutionary relative of alkaline phosphatases. ATX is found to be deep hydrophobic lipid-binding pocket that is around 15 Å. There is accommodationmonoacyl. Nevertheless, diacyl phospholipids are not accommodated. A depth at optimal for LPA (14:0) is observed (16). Subsequent studies show that lipid-binding pocket is perennially ‘open’. It indicates that LPC substrate has a permanent access to the active site.

论文代写:ATX蛋白的组成
This would drive catalysis through ‘substrate destabilization’, in which lowers the activation energy barrier of the phosphodiester hydrolysis reaction (16). ATX is found to hydrolyze the head groups of lysophospholipids. It is observed that lysophosphatidic acid (1 or 2-acyl-sn-glycerol-3-phosphate, LPA) acts with the sphingosylphosphorylcholine and yield sphingosine 1-phosphate (S1P) (17). On the other side of the structure, LPA and S1P are strong inhibitors of ATX. They have affinity to enzyme. There is 1000-fold higher than the usual TX substrates (18). ATX is known as the main source of blood LPA, however, not for S1P (19, 20). ATX is expressed in many organs in human, and its highest mRNA levels were detected in brain, ovary, nervous system, digestive racks and kidney. Relatively higher ATX mRNA levels are found in lymph nodes. At specifically,it is at high levels of concentration of endothelialvenules. Endothelial venues are an important control check into lymphocyte entry (21, 22).

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