变异链球菌SMU.2055蛋白晶体结构及其小分子抑制剂设计与筛选
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...
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| Published in | 华西口腔医学杂志 Vol. 33; no. 2; pp. 182 - 186 |
|---|---|
| Main Author | |
| Format | Journal Article |
| Language | Chinese |
| Published |
南方医科大学南方医院口腔科，南方医科大学口腔医学院，广州 510515%南开大学口腔医院·天津市口腔医院牙体牙髓病科，天津 300041%兰州大学药学院,兰州,730000
2015
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1000-1182 |
| DOI | 10.7518/hxkq.2015.02.016 |
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| Abstract | 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。 |
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| AbstractList | Q 51; 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。 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。 |
| Abstract_FL | ObjectiveThe?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?C2221,?with unit cell parameters of a=9.20nm, b=9.46nm, and c=19.39nm. 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?under-stand?the?structures?and?functions?of?proteins?from?S. mutans?at?the?atomic?level.?These?five?compounds?may?be?considered?as?effec-tive?inhibitors?to?SMU.2055.?The?virtual?model?of?small?mole-cule?inhibitors?we?built?will?lay?a?foundation?to?the?anticaries?research?based?on?the?crystal?structure?of?proteins. |
| Author | 陈晓丹 展秀荣 吴昕彧 赵春燕 赵望泓 |
| AuthorAffiliation | 南方医科大学南方医院口腔科、南方医科大学口腔医学院,广州510515 南开大学口腔医院·天津市口腔医院牙体牙髓病科,天津300041 兰州大学药学院,兰州730000 |
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| Author_FL | Zhan Xiurong Chen Xiaodan Zhao Wanghong Wu Xinyu Zhao Chunyan |
| Author_FL_xml | – sequence: 1 fullname: Chen Xiaodan – sequence: 2 fullname: Zhan Xiurong – sequence: 3 fullname: Wu Xinyu – sequence: 4 fullname: Zhao Chunyan – sequence: 5 fullname: Zhao Wanghong |
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| Copyright | Copyright © Wanfang Data Co. Ltd. All Rights Reserved. |
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| DOI | 10.7518/hxkq.2015.02.016 |
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| DocumentTitleAlternate | Crystal structure of SMU.2055 protein fromStreptococcus mutans and its small molecule inhibitors design and selec- tion |
| DocumentTitle_FL | Crystal structure of SMU.2055 protein fromStreptococcus mutans and its small molecule inhibitors design and selec- tion |
| EndPage | 186 |
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| GrantInformation_xml | – fundername: 国家自然科学基金资助项目; 广东省高校人才引进基金资助项目; 南方医科大学南方医院院长基金资助项目 funderid: (81050035); (C1030636); (2013B003) |
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| Keywords | small molecule inhibitors 小分子抑制剂 蛋白质晶体学 protein crystallo-graphy 变异链球菌 Streptococcus mutans |
| Language | Chinese |
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| Notes | 51-1169/R Streptococcus mutans;protein crystallo-graphy;small molecule inhibitors Chen Xiaodan, Zhan Xiurong, Wu Xinyu, Zhao Chunyan, Zhao Wanghong （1. Dept. of Stomatology, Nanfang Hospital, Southern Medical University; School of Stomatology, Southern Medical University, Guangzhou 510515, China; 2. Dept. of Endodontics, Tianjin Stomatologieal Hospital, Stomatological Hospital of Nankai University, Tianjin 300041, China,3. College of Pharmacy, Lanzhou Universtity, Lanzhou 730000, China） 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 |
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| PublicationTitle | 华西口腔医学杂志 |
| PublicationTitleAlternate | West China Journal of Stomatology |
| PublicationTitle_FL | West China Journal of Stomatology |
| PublicationYear | 2015 |
| Publisher | 南方医科大学南方医院口腔科，南方医科大学口腔医学院，广州 510515%南开大学口腔医院·天津市口腔医院牙体牙髓病科，天津 300041%兰州大学药学院,兰州,730000 |
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| SubjectTerms | 变异链球菌 小分子抑制剂 蛋白质晶体学 |
| Title | 变异链球菌SMU.2055蛋白晶体结构及其小分子抑制剂设计与筛选 |
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