Hussain Nadia, Muccee Fatima
Department of Pharmaceutical Sciences, College of Pharmacy, Al Ain University, Al Ain Campus, Al Ain 64141, United Arab Emirates.
AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi Campus, Abu Dhabi P. O. Box 112612, United Arab Emirates.
Saudi J Biol Sci. 2024 Apr;31(4):103939. doi: 10.1016/j.sjbs.2024.103939. Epub 2024 Feb 2.
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.
多发性硬化症（MS）是一种以神经元炎症和脱髓鞘为特征的神经退行性疾病。有证据表明，由于γ-氨基丁酸转氨酶（GABAT）的降解作用，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。多发性硬化症总是伴随着肠道细菌生态失调。在健康个体中，发现有 菌属，而在多发性硬化症患者中， 菌属和 菌属大量存在。尽管所有这些微生物都产生GABAT，但只有在多发性硬化症患者中，这种酶才会显著降解GABA。
本研究旨在对这些细菌的GABAT蛋白序列进行表征。
从Uniprot数据库中检索GABAT蛋白序列。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。
在健康个体的胃肠道（GIT）细菌中，GABAT蛋白存在于内膜中，α螺旋含量为（61%和62%），β折叠含量为（5%），具有4个螺旋细胞因子功能域。与多发性硬化症患者的GIT细菌酶相比，它具有更多的B细胞表位和更复杂的三维结构。
本研究可能使我们能够通过对病原菌进行定点诱变来修饰GABAT编码基因和酶，从而降低它们引发多发性硬化症的可能性。
