肺炎链球菌R6中Spr0934蛋白与铁色素相互作用机制的研究

Interaction mechanism between Spr0934 and ferrichrome in Streptococcus pneumoniae R6

目的探究肺炎链球菌R6中未知蛋白Spr0934与其潜在配体铁色素相互作用的机制。方法基于Uniprot数据库对目标蛋白Spr0934进行同源序列比对,筛选出与其同源性较高的候选蛋白;利用Spr0934蛋白结构与铁色素配体进行分子对接;分子动力学模拟技术检测铁色素被靶标蛋白结合之后引起的结构变化,并分析二者的结合机理。结果Spr0934与多个细菌蛋白具有较高同源性,其中铁色素结合蛋白4HMQ的活性中心与该蛋白相似性最高;分子对接的结果显示,铁色素与Spr0934的结合能量稳定在-6.27 kcal/mol,表明铁色素为潜在的配体分子;分子动力学模拟的结果证实,与apoSpr0934相比,该配体分子能让蛋白结构趋于稳定,蛋白整体波动性、溶剂可及表面积、氨基酸残基的灵活性均降低,二级结构各组分的比例更为合理。结论在Spr0934与铁色素可能的相互作用机制中,直接相互作用的位点为Asn-83、Tyr-133、Tyr-225和Arg-231,而Ala-82、Tyr-84、Trp-158和Phe-255起辅助作用。

Objective To investigate the interaction mechanism between hypothetical protein Spr0934 and its potential ligand ferrichrome(Fc)in Streptococcus pneumoniae R6.Methods Spr0934 sequence was used to perform homologous sequence alignment and to screen candidate proteins with high homology using UniProt database,while its structure was used for molecular docking with Fc ligand.Molecular dynamics simulation was used to detect the structural changes caused by the binding of Fc with the target protein,and the binding mechanism was analyzed.Results Spr0934 had a high homology with many bacterial proteins,with the highest similarity with active center of Fc binding protein 4HMQ.The results of molecular docking showed that the binding energy between Fc and Spr0934 was stable at-6.27 kcal/moL,indicating that Fc was a potential ligand.Compared with apo Spr0934,the results of molecular dynamics simulation revealed that the ligand stabilized the protein structure,and reduced the overall volatility,solvent accessible surface area and the flexibility of amino acid residues.The proportion of secondary protein structure was more reasonable.Conclusion In the interaction mechanism between Spr0934 and Fc,the direct interaction sites could be Asn-83,Tyr-133,Tyr-225,and Arg-231,while Ala-82,Tyr-84,Trp-158,and Phe-255 may be auxiliary.