Objective: The aim of this study is to analyze the three-dimensional crystal structure of SMU.2055 protein, a putative acetyltransferase from the major caries pathogen Streptococcus mutans (S. mutans). The design and selection of the structure-based small molecule inhibitors are also studied.
Methods: The three-dimensional crystal structure of SMU.2055 protein was obtained by structural genomics research methods of gene cloning and expression, protein purification with Ni²⁺-chelating affinity chromatography, crystal screening, and X-ray diffraction data collection. An inhibitor virtual model matching with its target protein structure was set up using computer-aided drug design methods, virtual screening and fine docking, and Libdock and Autodock procedures.
Results: The crystal of SMU.2055 protein was obtained, and its three-dimensional crystal structure was analyzed. This crystal was diffracted to a resolution of 0.23 nm. It belongs to orthorhombic space group C222(1), with unit cell parameters of a = 9.20 nm, b = 9.46 nm, and c = 19.39 nm. The asymmetric unit contained four molecules, with a solvent content of 56.7%. Moreover, five small molecule compounds, whose structure matched with that of the target protein in high degree, were designed and selected.
Conclusion: Protein crystallography research of S. mutans SMU.2055 helps to understand the structures and functions of proteins from S. mutans at the atomic level. These five compounds may be considered as effective inhibitors to SMU.2055. The virtual model of small molecule inhibitors we built will lay a foundation to the anticaries research based on the crystal structure of proteins.
目的: 研究变异链球菌UA159中SMU.2055蛋白的三维晶体结构，并基于其结构进行小分子抑制剂的设计与筛选。
方法: 运用结构基因组学研究方法，通过基因克隆和表达、蛋白质纯化、晶体筛选、晶体衍射数据收集，解析SMU.2055蛋白三维晶体结构，并运用计算机辅助药物设计方法，利用Libdock、Autodock两种程序，通过虚拟筛选和精确对接方式，建立与SMU.2055结构相匹配的小分子抑制剂虚拟模型。
结果: 获得SMU.2055蛋白结晶，解析SMU.2055蛋白三维晶体结构，晶体衍射率为0.23 nm，属于C2221空间群，晶胞参数为a=9.20 nm，b=9.46 nm，c=19.39 nm，溶剂体积分数为56.7%。设计并筛选出与SMU.2055蛋白结构匹配度高的5个小分子化合物。
结论: 变异链球菌SMU.2055蛋白质晶体学研究有助于从分子水平上深入了解变异链球菌蛋白质的结构和功能，筛选出的5个小分子化合物可能成为SMU.2055的有效小分子抑制剂，所建立的小分子抑制剂虚拟模型为基于蛋白质结构的防龋研究奠定基础。