進階搜尋


下載電子全文  
系統識別號 U0026-2907201312000900
論文名稱(中文) 整合磷酸化位點、酵素位點、蛋白質域資料至蛋白質結構變化資料庫
論文名稱(英文) Integrating phosphorylation site, catalytic site and protein domain information to a repository of protein structure changes
校院名稱 成功大學
系所名稱(中) 電機工程學系碩博士班
系所名稱(英) Department of Electrical Engineering
學年度 101
學期 2
出版年 102
研究生(中文) 江文豪
研究生(英文) Wen-Hao Chiang
學號 n26000305
學位類別 碩士
語文別 中文
論文頁數 41頁
口試委員 口試委員-曾大千
口試委員-吳謂勝
口試委員-劉宗霖
指導教授-張天豪
中文關鍵字 蛋白質  結構轉變  磷酸化  酵素  蛋白質域  均方根偏差值 
英文關鍵字 protein structure  conformational transition 
學科別分類
中文摘要 蛋白質是細胞中非常重要的功能分子,與各種生物分子間的反應,可產生一連串的生物機制。而蛋白質在反應的過程中,會產生許多的結構變化(conformational transitions),而這些結構變化點往往與生物機制有非常大的關係,進一步觀察並分析這些結構轉變點將會有助於更了解生物機制。
先前國立成功大學電機工程學系分子生醫資訊實驗室已建構了一個收集蛋白質的結合前結構(apo structure)與結合後結構(holo structure)的資料庫,Apo-Holo DataBase (AH-DB),使用Protein Data Bank(PDB)裡七萬多筆的結構檔,產生七十多萬組的蛋白質結構對,並且提供3D的分子模擬模型,讓使用者可以很容易從視覺上觀察蛋白質反應前後的結構,有助於觀察蛋白質反應前後結構變化。
這次本篇研究新增了四個生物上具有重要意義的要素:磷酸化位點(phosphorylation sites)、酵素位點(Catalytic Site)、蛋白質域(protein domain)以及提出一種對蛋白質結構變異量測的新方法:局部的均方根偏差值(local-root mean square deviation,L-RMSD),並從一個案例研究中舉證這兩項功能所提供的便利性以及其他的應用。
英文摘要 Protein is the so-called molecule machine which interacts with various molecules. These interactions are critical to biological processes. A protein before interaction is called “apo” state while after interaction is called “holo” state. Our recent study constructed the largest repository, Apo-Holo DataBase (AH-DB), of apo-holo structure pairs in the world, which enables researchers to understand protein interactions and their associated biological processes. This work is a following work of AH-DB. In this work, two enhancements have been done: (a) phosphorylation sites (b) catalytic sites (c) protein domain and (d) a novel measure of structural variation. A case study conducted in this work shows that the two enhancements make AH-DB capable to provide wider applications.
論文目次 目錄 1
圖目錄 3
第 一 章 緒論 4
第 二 章 相關研究 5
2.1蛋白質結構 5
2.1.1二級結構 5
2.1.2非穩定區和穩定區的結構轉變 6
2.2磷酸化作用 7
2.3 催化作用 7
2.4 相關資料庫 8
2.4.1 蛋白質資料庫 8
2.4.2 磷酸化位點資料庫 9
2.4.3 酵素位點資料庫 9
2.4.3 蛋白質域資料庫 10
2.4.4 蛋白質結構轉換資料庫 10
第 三 章 資料蒐集與實驗方法 12
3.1結合前後結構對 12
3.2結構的疊置演算法 15
3.2.1 AH-DB複合物結構疊置 15
3.2.2局部均方根偏差值(L-RMSD) 15
3.3 資料蒐集與整合 16
3.3.1 磷酸化位點(Phosphorylation site) 16
3.3.2酵素位點(Catalytic site) 18
3.3.3 蛋白質域(Pfam domain) 18
3.4 資料應用與資料呈現 18
3.4.1 磷酸化位點(Phosphorylation site) 18
3.4.2酵素位點(Catalytic site) 20
3.4.3 蛋白質域(Pfam domain) 21
第 四 章 網站使用介面與個案分析及比較 24
4.1使用者介面 24
4.1.1首頁 25
4.1.2搜尋頁 27
4.1.3 結構序列頁 28
4.2個案分析 32
4.2.1超氧化物歧化酶(SOD1) 32
4.2.2熱休克蛋白(Hsp90) 35
第 五 章 結論與未來展望 39
5.1 結論 39
5.2 未來展望 39
參考文獻 40
參考文獻 1. Chang DT-H, Yao T-J, Fan C-Y, Chiang C-Y, Bai Y-H: AH-DB: collecting protein structure pairs before and after binding. Nucleic acids research 2012, 40(D1):D472-D478.
2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat T, Weissig H, Shindyalov IN, Bourne PE: The protein data bank. Nucleic acids research 2000, 28(1):235-242.
3. Hanson RM: Jmol-a paradigm shift in crystallographic visualization. Journal of Applied Crystallography 2010, 43(5):1250-1260.
4. Mathews CK, Van Holde KE, Ahern KG: Biochemistry, 3. edn; 2000.
5. Collins MO, Yu L, Campuzano I, Grant SG, Choudhary JS: Phosphoproteomic analysis of the mouse brain cytosol reveals a predominance of protein phosphorylation in regions of intrinsic sequence disorder. Molecular & Cellular Proteomics 2008, 7(7):1331-1348.
6. Reeves R, Beckerbauer L: HMGI/Y proteins: flexible regulators of transcription and chromatin structure. Biochimica et biophysica acta 2001, 1519(1-2):13.
7. Barford D, Das AK, Egloff M-P: The structure and mechanism of protein phosphatases: insights into catalysis and regulation. Annual review of biophysics and biomolecular structure 1998, 27(1):133-164.
8. Chang C, Stewart RC: The two-component system regulation of diverse signaling pathways in prokaryotes and eukaryotes. Plant physiology 1998, 117(3):723-731.
9. Cozzone AJ: Protein phosphorylation in prokaryotes. Annual Reviews in Microbiology 1988, 42(1):97-125.
10. Stock J, Ninfa A, Stock A: Protein phosphorylation and regulation of adaptive responses in bacteria. Microbiological reviews 1989, 53(4):450.
11. Bairoch A, Apweiler R, Wu CH, Barker WC, Boeckmann B, Ferro S, Gasteiger E, Huang H, Lopez R, Magrane M: The universal protein resource (UniProt). Nucleic acids research 2005, 33(suppl 1):D154-D159.
12. Dinkel H, Chica C, Via A, Gould CM, Jensen LJ, Gibson TJ, Diella F: Phospho. ELM: a database of phosphorylation sites—update 2011. Nucleic acids research 2011, 39(suppl 1):D261-D267.
13. Zanzoni A, Ausiello G, Via A, Gherardini PF, Helmer-Citterich M: Phospho3D: a database of three-dimensional structures of protein phosphorylation sites. Nucleic acids research 2007, 35(suppl 1):D229-D231.
14. Zanzoni A, Carbajo D, Diella F, Gherardini PF, Tramontano A, Helmer-Citterich M, Via A: Phospho3D 2.0: an enhanced database of three-dimensional structures of phosphorylation sites. Nucleic acids research 2011, 39(suppl 1):D268-D271.
15. Porter CT, Bartlett GJ, Thornton JM: The Catalytic Site Atlas: a resource of catalytic sites and residues identified in enzymes using structural data. Nucleic acids research 2004, 32(suppl 1):D129-D133.
16. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, Griffiths‐Jones S, Khanna A, Marshall M, Moxon S, Sonnhammer EL: The Pfam protein families database. Nucleic acids research 2004, 32(suppl 1):D138-D141.
17. Lobanov MY, Shoemaker BA, Garbuzynskiy SO, Fong JH, Panchenko AR, Galzitskaya OV: ComSin: database of protein structures in bound (complex) and unbound (single) states in relation to their intrinsic disorder. Nucleic acids research 2010, 38(Database issue):D283-287.
18. Marchler-Bauer A, Lu S, Anderson JB, Chitsaz F, Derbyshire MK, DeWeese-Scott C, Fong JH, Geer LY, Geer RC, Gonzales NR et al: CDD: a Conserved Domain Database for the functional annotation of proteins. Nucleic acids research 2011, 39(Database issue):D225-229.
19. Zhang Z: Iterative point matching for registration of
free-form curves and surfaces. Int J Comput Vision 1994, 13:119 - 152.
20. Theobald DL, Wuttke DS: THESEUS: maximum likelihood superpositioning and analysis of macromolecular structures. Bioinformatics (Oxford, England) 2006, 22(17):2171-2172.
21. Jmol [http://www.jmol.org/]
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2018-08-20起公開。
  • 同意授權校外瀏覽/列印電子全文服務,於2018-08-20起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw