Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, P.O. Box 71348-14366, Shiraz, Iran.
Department of Microbiology, School of Medicine, Fasa University of Medical Sciences, P.O. Box 74616-86688, Fasa, Iran.
Recent Pat Biotechnol. 2020;14(3):235-246. doi: 10.2174/1872208314666200324114441.
Arginine deiminase is a bacterial enzyme, which degrades L-arginine. Some human cancers such as hepatocellular carcinoma (HCC) and melanoma are auxotrophic for arginine. Therefore, PEGylated arginine deiminase (ADI-PEG20) is a good anticancer candidate with antitumor effects. It causes local depletion of L-arginine and growth inhibition in arginineauxotrophic tumor cells. The FDA and EMA have granted orphan status to this drug. Some recently published patents have dealt with this enzyme or its PEGylated form.
Due to increasing attention to it, we aimed to evaluate and compare 30 arginine deiminase proteins from different bacterial species through in silico analysis.
The exploited analyses included the investigation of physicochemical properties, multiple sequence alignment (MSA), motif, superfamily, phylogenetic and 3D comparative analyses of arginine deiminase proteins thorough various bioinformatics tools.
The most abundant amino acid in the arginine deiminase proteins is leucine (10.13%) while the least amino acid ratio is cysteine (0.98%). Multiple sequence alignment showed 47 conserved patterns between 30 arginine deiminase amino acid sequences. The results of sequence homology among 30 different groups of arginine deiminase enzymes revealed that all the studied sequences located in amidinotransferase superfamily. Based on the phylogenetic analysis, two major clusters were identified. Considering the results of various in silico studies; we selected the five best candidates for further investigations. The 3D structures of the best five arginine deiminase proteins were generated by the I-TASSER server and PyMOL. The RAMPAGE analysis revealed that 81.4%-91.4%, of the selected sequences, were located in the favored region of arginine deiminase proteins.
The results of this study shed light on the basic physicochemical properties of thirty major arginine deiminase sequences. The obtained data could be employed for further in vivo and clinical studies and also for developing the related therapeutic enzymes.
精氨酸脱亚氨酶是一种细菌酶，可分解 L-精氨酸。一些人类癌症，如肝细胞癌（HCC）和黑色素瘤，对精氨酸具有辅助营养需求。因此，聚乙二醇化精氨酸脱亚氨酶（ADI-PEG20）是一种具有抗肿瘤作用的良好抗癌候选药物。它会导致局部 L-精氨酸耗竭，并抑制精氨酸辅助营养需求的肿瘤细胞生长。FDA 和 EMA 已授予该药物孤儿药地位。最近公布的一些专利涉及该酶或其聚乙二醇化形式。
由于对其关注度的增加，我们旨在通过计算机分析评估和比较来自不同细菌物种的 30 种精氨酸脱亚氨酶蛋白。
利用的分析包括通过各种生物信息学工具调查精氨酸脱亚氨酶蛋白的理化性质、多序列比对（MSA）、基序、超家族、系统发育和 3D 比较分析。
精氨酸脱亚氨酶蛋白中最丰富的氨基酸是亮氨酸（10.13%），而最少的氨基酸比例是半胱氨酸（0.98%）。多序列比对显示 30 种精氨酸脱亚氨酶氨基酸序列之间有 47 个保守模式。30 组不同的精氨酸脱亚氨酶酶序列之间的序列同源性结果表明，所有研究的序列都位于氨甲酰转移酶超家族中。基于系统发育分析，确定了两个主要簇。考虑到各种计算机研究的结果；我们选择了五个最佳候选者进行进一步研究。通过 I-TASSER 服务器和 PyMOL 生成了五个最佳精氨酸脱亚氨酶蛋白的 3D 结构。RAMPAGE 分析表明，81.4%-91.4%的选定序列位于精氨酸脱亚氨酶蛋白的有利区域。
本研究结果阐明了 30 种主要精氨酸脱亚氨酶序列的基本理化性质。获得的数据可用于进一步的体内和临床研究，也可用于开发相关的治疗性酶。
