基于分子对接技术筛选水稻黄单胞菌CSE抑制剂

Inhibitor screening of Xanthomonas oryzae pv. oryzae CSE based on molecular docking technology

由水稻黄单胞菌(Xoo)引起的水稻白叶枯病通常会给水稻带来严重危害;由于抗生素类药物的广泛使用,Xoo出现了耐药性.细菌通过体内的胱硫醚-γ-裂解酶(CSE)产生内源性硫化氢(H2S)是其增强耐药性的重要方式.为降低Xoo的耐药性,基于分子对接技术,以Xoo体内的CSE为靶标,从68个吲哚类生物碱中虚拟筛选CSE抑制剂.结果显示,化合物1-hydroxyrutaecarpine、indican和strictosamide对靶蛋白的亲和力分别为-36.40、-35.15和-34.30 kJ·mol^(-1),均低于参考化合物NL3(-33.89 kJ·mol^(-1)).上述化合物的部分结构均能嵌入蛋白活性空腔并与周围氨基酸产生较为稳定的相互作用.由此推测化合物1-hydroxyrutaecarpine、indican和strictosamide可能会对Xoo体内的CSE产生一定的抑制作用.

Rice bacterial blight caused by Xanthomonas oryzae pv. oryzae(Xoo) usually brings serious harm to rice, however, the resistant Xoo has arisen due to the wide use of antibiotics. Production of endogenous hydrogen sulfide(H2S) by cystathionine-γ-lyase(CSE) in Xoo is an important way to enhance its resistance. In order to reduce the drug resistance of Xoo, the CSE in Xoo was selected as the target to screen CSE inhibitor from 68 indole alkaloids based on molecular docking technology. The results showed that the affinity of 1-ydroxyrutaecarpine, indican and strictosamide to CSE were-36.40,-35.15 and-34.30 kJ·mol^(-1), respectively, which were lower than those to the reference compound NL3(-33.89 kJ·mol^(-1)). Some structures of these compounds could be embedded into the protein active cavity and interact stably with the surrounding amino acids. Therefore, it is speculated that the CSE of Xoo can be inhibited by 1-hydroxyrutaecarpine, indican and strictosamide to some extent.