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In-silico characterization of GABAT protein found in gut-brain axis associated bacteria of healthy individuals and multiple sclerosis patients
Saudi Journal of Biological Sciences ( IF 4.4 ) Pub Date : 2024-02-02 , DOI: 10.1016/j.sjbs.2024.103939
Nadia Hussain , Fatima Muccee

Multiple sclerosis (MS) is a neurodegenerative disease characterized by inflammation and demyelination of neurons. There is evidence to suggest that level of a neurotransmitter gamma-aminobutyric acid (GABA), due to the degradation by γ-aminobutyric acid transaminase (GABAT), is reduced in certain areas of the brain in MS patients. MS is always accompanied by gut bacteria dysbiosis. In healthy individuals, sp. while in MS patients sp. and are found abundantly. Although all these microbes produce GABAT but only in MS patients this enzyme significantly degrades GABA. Present study is an attempt to characterize the GABAT protein sequences of these bacteria. Sequences of GABAT protein were retrieved from Uniprot database. Sequences were analyzed by Protparam, Gneg-mPLoc, SOSUI, PFP-FunDSeqE, Pepwheel program, PROTEUS and Alphafold and SAVES servers, MEME suite and HDOCK server. In healthy individuals gastrointestinal tract (GIT) bacteria, GABAT protein was present in inner-membrane with α helix content (61 and 62%) and β sheet content (5%), 4-helical cytokines functional domains. It has greater number of B-cell epitopes and more complex 3D configuration as compared to MS patients GIT bacterial enzymes. Present study might enable us to modify the GABAT encoding gene and enzyme through site-directed mutagenesis in pathogenic bacteria thus reducing their potential of causing MS.

中文翻译:

健康个体和多发性硬化症患者肠脑轴相关细菌中发现的 GABAT 蛋白的计算机表征

多发性硬化症(MS)是一种神经退行性疾病,其特征是神经元炎症和脱髓鞘。有证据表明,由于 γ-氨基丁酸转氨酶 (GABAT) 的降解,多发性硬化症患者大脑某些区域的神经递质 γ-氨基丁酸 (GABA) 水平降低。MS 总是伴随着肠道细菌失调。在健康个体中,sp。而在多发性硬化症患者中。并大量被发现。尽管所有这些微生物都会产生 GABAT,但只有在多发性硬化症患者中,这种酶才会显着降解 GABA。本研究试图表征这些细菌的 GABAT 蛋白序列。GABAT 蛋白的序列从 Uniprot 数据库中检索。通过 Protparam、Gneg-mPLoc、SOSUI、PFP-FunDSeqE、Pepwheel 程序、PROTEUS 和 Alphafold 以及 SAVES 服务器、MEME 套件和 HDOCK 服务器对序列进行分析。在健康个体胃肠道(GIT)细菌中,GABAT蛋白存在于内膜中,具有α螺旋含量(61%和62%)和β折叠含量(5%),4螺旋细胞因子功能域。与多发性硬化症患者胃肠道细菌酶相比,它具有更多数量的 B 细胞表位和更复杂的 3D 结构。目前的研究可能使我们能够通过病原菌的定点诱变来修改 GABAT 编码基因和酶,从而降低其引起 MS 的可能性。
更新日期:2024-02-02
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