亚洲自由杆菌阳离子氨基酸结合蛋白的特征及确定潜在抑制分子的硅学研究

IF 1.9 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY The Protein Journal Pub Date : 2024-09-21 DOI:10.1007/s10930-024-10233-w
Sapna Lonare, Deena Nath Gupta, Harry Kaur, Surabhi Rode, Shalja Verma, Mrugendra Gubyad, Dilip Kumar Ghosh, Pravindra Kumar, Ashwani Kumar Sharma
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引用次数: 0

摘要

阳离子氨基酸结合蛋白(CLasArgBP)是白色念珠菌(CLas)中两种氨基酸结合受体之一,主要在柑橘类果蝇中表达,是 ATP 结合盒转运系统的一部分。本研究介绍了利用各种生物物理技术对 CLasArgBP 进行的表征,以及通过虚拟筛选和 MD 模拟确定潜在的 CLasArgBP 抑制剂分子的硅学研究。此外,还进行了植物体内研究,以评估所选抑制剂对受黄龙病感染的莫桑比植物的影响。结果表明,CLasArgBP 对精氨酸、组氨酸和赖氨酸具有明显的特异性。表面等离子体共振(SPR)研究表明,与组氨酸和赖氨酸(Kd 分别为 15 µΜ 和 26 µΜ)相比,精氨酸的结合亲和力最高(Kd 为 0.14 µM)。同样,差示扫描量热法(DSC)研究表明,与组氨酸和赖氨酸相比,CLasArgBP 对精氨酸的稳定性更高。通过硅学研究,N(ω)-硝基-L-精氨酸、γ-羟基-L-精氨酸和巨氨酸成为先导化合物,与精氨酸相比,它们具有更高的结合能和稳定性。SPR 报告显示,相对于精氨酸,N(Ω)-硝基-L-精氨酸和γ-羟基-L-精氨酸的结合亲和力更高(Kd 分别为 0.038 µΜ 和 0.061 µΜ)。DSC 研究表明,CLasArgBP 与所选抑制剂复合物的热稳定性增强。环二色性和荧光研究表明,与精氨酸相比,CLasArgBP 与选定的抑制剂发生了明显的构象变化。植物体内研究表明,与对照植物相比,处理植物体内的 CLas 滴度大幅下降。总之,该研究首次全面描述了来自 CLas 的阳离子氨基酸结合蛋白的特性,并将其作为控制 HLB 疾病的潜在药物靶标。
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Characterization of Cationic Amino Acid Binding Protein from Candidatus Liberibacter Asiaticus and in Silico Study to Identify Potential Inhibitor Molecules

Cationic amino acid binding protein (CLasArgBP), one of the two amino acid binding receptor in Candidatus Liberibacter asiaticus (CLas), is predominately expressed in citrus psyllids as a part of ATP-binding cassette transport system. The present study describes characterization of CLasArgBP by various biophysical techniques and in silico study, to identify potential inhibitor molecules against CLasArgBP through virtual screening and MD simulations. Further, in planta study was carried out to assess the effect of selected inhibitors on Huanglongbing infected Mosambi plants. The results showed that CLasArgBP exhibits pronounced specificity for arginine, histidine and lysine. Surface plasmon resonance (SPR) study reports highest binding affinity for arginine (Kd, 0.14 µM), compared to histidine and lysine (Kd, 15 µΜ and 26 µΜ, respectively). Likewise, Differential Scanning Calorimetry (DSC) study showed higher stability of CLasArgBP for arginine, compared to histidine and lysine. N(omega)-nitro-L-arginine, Gamma-hydroxy-L-arginine and Gigartinine emerged as lead compounds through in silico study displaying higher binding energy and stability compared to arginine. SPR reports elevated binding affinities for N(omega)-nitro-L-arginine and Gamma-hydroxy-L-arginine (Kd, 0.038 µΜ and 0.061 µΜ, respectively) relative to arginine. DSC studies showed enhanced thermal stability for CLasArgBP in complex with selected inhibitors. Circular dichroism and fluorescence studies showed pronounced conformational changes in CLasArgBP with selected inhibitors than with arginine. In planta study demonstrated a substantial decrease in CLas titer in treated plants as compared to control plants. Overall, the study provides the first comprehensive characterization of cationic amino acid binding protein from CLas, as a potential drug target to manage HLB disease.

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The Protein Journal
The Protein Journal 生物-生化与分子生物学
CiteScore
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期刊介绍: The Protein Journal (formerly the Journal of Protein Chemistry) publishes original research work on all aspects of proteins and peptides. These include studies concerned with covalent or three-dimensional structure determination (X-ray, NMR, cryoEM, EPR/ESR, optical methods, etc.), computational aspects of protein structure and function, protein folding and misfolding, assembly, genetics, evolution, proteomics, molecular biology, protein engineering, protein nanotechnology, protein purification and analysis and peptide synthesis, as well as the elucidation and interpretation of the molecular bases of biological activities of proteins and peptides. We accept original research papers, reviews, mini-reviews, hypotheses, opinion papers, and letters to the editor.
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