College of Life Science and Key Laboratory of Ministry of Education, Jiangxi Normal University, Nanchang, Jiangxi 330022, China.
College of Life Science and Key Laboratory of Ministry of Education, Jiangxi Normal University, Nanchang, Jiangxi 330022, China.
Int J Biol Macromol. 2019 Feb 1;122:1244-1252. doi: 10.1016/j.ijbiomac.2018.09.077. Epub 2018 Sep 15.
α-Glucosidase is a critical enzyme associated with diabetes mellitus, and the inhibitors of the enzyme play important roles in the treatment of the disease. In this study, the inhibitory effect and mechanism of rifampicin on α-glucosidase were investigated by multispectroscopic methods along with molecular docking technique. The results showed that rifampicin inhibited α-glucosidase activity prominently (IC = 135 ± 1.2 μM) in a reversible and competitive-type manner. The fluorescence intensity of α-glucosidase was quenched by rifampicin through forming rifampicin-α-glucosidase complex in a static procedure. And the formation of the rifampicin-α-glucosidase complex was driven spontaneously by hydrophobic forces and hydrogen bonds. The results obtained from molecular docking further indicated that hydrophobic forces were formed between rifampicin and amino acid residues Phe 173, Pro151, and hydrogen bonds were generated by the interactions of rifampicin with residues Ser 180, Asn 414, Gly160, and Gly161 of α-glucosidase. Moreover, it was found that the binding of rifampicin to α-glucosidase could alter the conformation of the enzyme to make it steady, and the binding distance was estimated to be 1.02 nm. Therefore, this study confirmed a novel α-glucosidase inhibitor and possibly contributed to the improvement of newfangled anti-diabetic agent.
α-葡萄糖苷酶是与糖尿病密切相关的关键酶，该酶的抑制剂在疾病治疗中发挥着重要作用。本研究采用多种光谱方法结合分子对接技术，研究了利福平对α-葡萄糖苷酶的抑制作用及机制。结果表明，利福平以可逆和竞争型方式显著抑制α-葡萄糖苷酶活性（IC = 135 ± 1.2 μM）。利福平通过形成静态过程中的利福平-α-葡萄糖苷酶复合物来猝灭α-葡萄糖苷酶的荧光强度。并且，复合物的形成是由疏水作用力和氢键驱动的自发过程。分子对接的结果进一步表明，疏水作用力形成于利福平与氨基酸残基 Phe 173、Pro151 之间，氢键则由利福平与α-葡萄糖苷酶残基 Ser 180、Asn 414、Gly160 和 Gly161 的相互作用产生。此外，还发现利福平与α-葡萄糖苷酶的结合可以改变酶的构象使其稳定，结合距离估计为 1.02nm。因此，本研究证实了一种新型的α-葡萄糖苷酶抑制剂，可能有助于开发新型抗糖尿病药物。
