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.

Eis（增强细胞内存活）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（GCN5 相关 N-乙酰转移酶家族）家族。Eis 的酶活性导致卡那霉素乙酰化，从而损害药物的作用。在本研究中，我们表达并纯化了重组 Eis (rEis)，以确定 Eis 及其潜在抑制剂的酶活性。使用滑动增强精确对接来与所选配体进行分子对接。与其他配体相比，槲皮素被发现与 Eis 相互作用，最大结合亲和力为 -8.379 kcal/mol。槲皮素显示Eis中带正电荷的氨基酸精氨酸与槲皮素的芳香环之间通过π-阳离子相互作用发生特异性相互作用。此外，还研究了在槲皮素存在和不存在的情况下 rEis 对卡那霉素 A 抗生素活性的影响。观察到rEis氨基糖苷乙酰转移酶的活性随着槲皮素浓度的增加而降低。纸片扩散测定的结果证实，增加槲皮素浓度会抑制 rEis 蛋白活性。总之，槲皮素可能作为一种潜在的 Eis 抑制剂。