Targeting Aminoglycoside Acetyltransferase Activity of Mycobacterium tuberculosis (H37Rv) Derived Eis (Enhanced Intracellular Survival) Protein with Quercetin

IF 1.9 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

The Protein Journal Pub Date : 2023-11-06 DOI:10.1007/s10930-023-10165-x

Logesh Radhakrishnan, Rahul Dani, Irfan Navabshan, Shazia Jamal, Neesar Ahmed

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引用次数: 0

Abstract

Eis (Enhanced intracellular survival) protein is an aminoglycoside acetyltransferase enzyme classified under the family – GNAT (GCN5-related family of N-acetyltransferases) secreted by Mycobacterium tuberculosis (Mtb). The enzymatic activity of Eis results in the acetylation of kanamycin, thereby impairing the drug’s action. In this study, we expressed and purified recombinant Eis (rEis) to determine the enzymatic activity of Eis and its potential inhibitor. Glide-enhanced precision docking was used to perform molecular docking with chosen ligands. Quercetin was found to interact Eis with a maximum binding affinity of -8.379 kcal/mol as compared to other ligands. Quercetin shows a specific interaction between the positively charged amino acid arginine in Eis and the aromatic ring of quercetin through π-cation interaction. Further, the effect of rEis was studied on the antibiotic activity of kanamycin A in the presence and absence of quercetin. It was observed that the activity of rEis aminoglycoside acetyltransferase decreased with increasing quercetin concentration. The results from the disk diffusion assay confirmed that increasing the concentration of quercetin inhibits the rEis protein activity. In conclusion, quercetin may act as a potential Eis inhibitor.

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槲皮素靶向结核分枝杆菌（H37Rv）衍生的细胞内存活增强蛋白的氨基糖苷乙酰转移酶活性。

Eis（Enhanced cellular survival）蛋白是一种氨基糖苷乙酰转移酶，属于结核分枝杆菌（Mtb）分泌的GNAT家族（GCN5相关的N-乙酰转移酶家族）。艾斯的酶活性导致卡那霉素的乙酰化，从而削弱药物的作用。在本研究中，我们表达并纯化了重组Eis（rEis），以测定Eis的酶活性及其潜在的抑制剂。Glide增强精密对接用于与选定的配体进行分子对接。与其他配体相比，槲皮素与Eis相互作用的最大结合亲和力为-8.379 kcal/mol。槲皮素通过π-阳离子相互作用，表现出Eis中带正电荷的氨基酸精氨酸与槲皮素的芳香环之间的特异性相互作用。此外，研究了在槲皮素存在和不存在的情况下，rEis对卡那霉素A的抗生素活性的影响。随着槲皮素浓度的增加，rEis氨基糖苷乙酰转移酶活性降低。来自盘扩散测定的结果证实，增加槲皮素的浓度抑制rEis蛋白活性。总之，槲皮素可能是一种潜在的Eis抑制剂。

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来源期刊

The Protein Journal 生物-生化与分子生物学

CiteScore

5.20

自引率

0.00%

发文量

审稿时长

12 months

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.