日本血吸虫硫氧还蛋白谷胱甘肽还原酶同源建模及功能分析

目的 对日本血吸虫硫氧还蛋白谷胱甘肽还原酶(TGR)进行结构及功能分析。方法 基于结构序列比较利用Swiss-Pdbviewer构建了日本血吸虫的TGR同源结构模型,并对模型进行结构评估;分析日本血吸虫TGR与底物结合时可能的位点,比较这些位点在不同来源TGR中的异同。 结果 日本血吸虫TGR结构在PROCHECK评估中被证实可靠;位点比较分析表明NADPH、GDS结合区是保守的位点;GSH结合区存在特异性。结论 作用于GDS、NADPH结合区的其它来源的TGR抑制剂可能对日本血吸虫TGR也有作用;GSH结合区是设计寄生虫TGR特异性抑制剂的潜在靶点之一;TGR的C末端对电子传递起着重要作用并可能参与底物的结合,因而阻断日本血吸虫TGR的C末端摆动的抑制剂将可能有效地抑制日本血吸虫TGR活性。

Homologous modeling and function analysis on thioredoxin glutathione reductase from Schistosoma japonicum

To explore the structure and function of thioredoxin glutathione reductase （TGR） from Schistosoma j aponi-cum ,the homologous model of TGR in Schistosoma j aponicum was constructed by Swiss-Pdbviewer based on sequence and structure alignment .The potential substrates binding sites of TGR were analyzed and these sites of various TGRs were also as-sessed .Our results showed that the homologous model of Schistosoma japonicum TGR based on Schistosoma mansoni TGR structure was proved to be reasonable by PROCHECK program .Analysis of binding sites showed that NADPH and GDS bind-ing sites were conservative sites and GSH binding site was a specific site for parasite .Our data suggested that inhibitors which work in NADPH and GDS binding sites of other various TGRs may also interact with TGR form Schistosoma j aponicum .GSH binding region might be one of the potential targets for design of specific inhibitors of parasite TGRs .In addition ,C-terminal of TGR plays an important role in electron transfer and may participate in the binding of the substrate .Thus compound inhibiting swing of C-terminal could effectively restrain Schistosoma j aponicum TGR activity .