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Structure-Based Immunogenicity Prediction of Uricase from Fungal (Aspergillus flavus), Bacterial (Bacillus subtillis) and Mammalian Sources Using Immunoinformatic Approach.
The Protein Journal ( IF 3 ) Pub Date : 2020-03-27 , DOI: 10.1007/s10930-020-09886-0
Shikha Tripathi 1 , Jyotsna Parmar 1 , Awanish Kumar 1
Affiliation  

Gout is a common rheumatic condition caused due to increase in serum uric acid level (hyperuricemia). Uricase is for lowering the level of uric acid but unfortunately, it is not produced in humans due to evolutionary changes. Therefore, it is administered to humans from outside in case of the high uric acid level in blood. A different formulation of uricase from bacterial, fungal, and mammalian sources is present in the market for the treatment of hyperuricemia conditions. Uricase formulation showed immunogenic response due to the occurrence of hypersensitivity reaction during the treatment that results in poor patient compliance. The purpose of this study was to clarify the variation of Uricase immunogenicity from different sources. We have used some immunoinformatic approaches to analyze and understand some structural aspects of immunogenic and allergenic epitopes of Uricase by calculation of relative frequency for eleven global alleles. As per our knowledge, this is the first immunoinformatic study of Uricase (structural based immunogenicity prediction) that deciphered the high immunogenic nature of Uricase but no significant difference in immunogenicity was found among Uricase isolated from Aspergillus flavus, Bacillus subtillis, and mammalian source. This study gives a further lead to develop some methods (include bioengineering of less immunogenic version of the uricase or utilizing the homologous enzymes) for minimizing immune response or search new sources of uricase that could be less or non-immunogenic.

中文翻译:

使用免疫信息学方法从真菌(黄曲霉),细菌(枯草芽孢杆菌)和哺乳动物来源的尿酸酶进行基于结构的免疫原性预测。

痛风是由于血清尿酸水平升高(高尿酸血症)引起的常见风湿病。尿酸酶是用于降低尿酸的水平,但是不幸的是,由于进化的变化,尿酸酶不是在人体内产生的。因此,在血液中尿酸水平高的情况下,它是从外面施用于人类的。市场上存在用于治疗高尿酸血症的尿酸酶的不同制剂,其来源是细菌,真菌和哺乳动物。尿酸酶制剂由于治疗期间发生超敏反应而导致免疫原性应答,导致患者顺应性差。这项研究的目的是阐明来自不同来源的尿酸酶免疫原性的变化。我们已经使用一些免疫信息学方法通过计算11个全局等位基因的相对频率来分析和了解尿酸酶的免疫原性和变应原性表位的某些结构方面。据我们所知,这是尿酸酶的第一项免疫信息学研究(基于结构的免疫原性预测),该研究破译了尿酸酶的高免疫原性,但在从黄曲霉,枯草芽孢杆菌和哺乳动物来源。这项研究为进一步开发一些方法(包括对免疫原性较低的尿酸酶版本进行生物工程或利用同源酶)以最大程度地减少免疫反应或寻找可能较少或无免疫原性的尿酸酶新来源提供了帮助。
更新日期:2020-03-27
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