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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78101完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳平 | |
| dc.contributor.author | Pei-Yu Huang | en |
| dc.contributor.author | 黃珮瑜 | zh_TW |
| dc.date.accessioned | 2021-07-11T14:42:16Z | - |
| dc.date.available | 2021-11-02 | |
| dc.date.copyright | 2016-11-02 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-18 | |
| dc.identifier.citation | 1. Davey, M. J.; O'Donnell, M. Mechanisms of DNA replication. Curr. Opin. Chem. Biol. 2000, 4, 581.
2. Harlow, E.; Crawford, L. V.; Pim, D. C.; Williamson, N. M. Monoclonal antibodies specific for simian virus 40 tumor antigens. J. Virol. 1981, 39, 861. 3. Palmer, C. N. A.; Irvine, A. D.; Terron-Kwiatkowski, A.; Zhao, Y. W.; Liao, H. H.; Lee, S. P.; Goudie, D. R.; Sandilands, A.; Campbell, L. E.; Smith, F. J. D.; O'Regan, G. M.; Watson, R. M.; Cecil, J. E.; Bale, S. J.; Compton, J. G.; DiGiovanna, J. J.; Fleckman, P.; Lewis-Jones, S.; Arseculeratne, G.; Sergeant, A.; Munro, C. S.; El Houate, B.; McElreavey, K.; Halkjaer, L. B.; Bisgaard, H.; Mukhopadhyay, S.; McLean, W. H. I. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat. Genet. 2006, 38, 441. 4. Goodsell, D. S.; Olson, A. J. Structural symmetry and protein function. Annu. Rev. Biophys. Biomol. Struct. 2000, 29, 105. 5. Rayment, I.; Holden, H. M.; Whittaker, M.; Yohn, C. B.; Lorenz, M.; Holmes, K. C.; Milligan, R. A. Structure of the actin-myosin complex and its implications for muscle contraction. Science 1993, 261, 58. 6. Dengjel, J.; Kratchmarova, I.; Blagoev, B. Receptor tyrosine kinase signaling: a view from quantitative proteomics. Mol. BioSyst. 2009, 5, 1112. 7. Brivanlou, A. H.; Darnell, J. E. Signal transduction and the control of gene expression. Science 2002, 295, 813. 8. Benkovic, S. J.; Hammes-Schiffer, S. A perspective on enzyme catalysis. Science 2003, 301, 1196. 9. Holm, L.; Sander, C. Protein structure comparison by alignment of distance matrices. J. Mol. Biol. 1993, 233, 123. 10. Pauling, L.; Corey, R. B. The planarity of the amide group in polypeptides. J. Am. Chem. Soc. 1952, 74, 3964. 11. Ramachandran, G. N.; Ramakrishnan, C.; Sasisekharan, V. Stereochemistry of polypeptide chain configurations. J. Mol. Biol. 1963, 7, 95. 12. Schellman, J. A.; Schellman, C. G. Kaj Ulrik Linderstrom-Lang (1896-1959). Protein Sci. 1997, 6, 1092. 13. Kubo, Y.; Reuveny, E.; Slesinger, P. A.; Jan, Y. N.; Jan, L. Y. Primary structure and functional expression of a rat G-protein-coupled muscarinic potassium channel. Nature 1993, 364, 802. 14. Leopold, P. E.; Montal, M.; Onuchic, J. N. Protein folding funnels: a kinetic approach to the sequence-structure relationship. Proc. Natl. Acad. Sci. U. S. A. 1992, 89, 8721. 15. Kabsch, W.; Sander, C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 1983, 22, 2577. 16. Compton, L. A.; Johnson, W. C. Analysis of protein circular dichroism spectra for secondary structure using a simple matrix multiplication. Anal. Biochem. 1986, 155, 155. 17. Pauling, L.; Corey, R. B.; Branson, H. R. The structure of proteins: two hydrogen-bonded helical configurations of the polypeptide chain. Proc. Natl. Acad. Sci. U.S.A. 1951, 37, 205. 18. Ramirez-Alvarado, M.; Kortemme, T.; Blanco, F. J.; Serrano, L. β-Hairpin and β-sheet formation in designed linear peptides. Bioorg. Med. Chem. 1999, 7, 93. 19. Dill, K. A. Dominant forces in protein folding. Biochemistry 1990, 29, 7133. 20. Makhatadze, G. I.; Loladze, V. V.; Ermolenko, D. N.; Chen, X. F.; Thomas, S. T. Contribution of surface salt bridges to protein stability: guidelines for protein engineering. J. Mol. Biol. 2003, 327, 1135. 21. Barlow, D. J.; Thornton, J. M. Ion-pairs in proteins. J. Mol. Biol. 1983, 168, 867. 22. Trikulenko, A. V. Role of hydrophobic interactions in protein chain folding during biosynthesis. Biochemistry 1998, 63, 564. 23. Favrin, G.; Irback, A.; Wallin, S. Folding of a small helical protein using hydrogen bonds and hydrophobicity forces. Proteins 2002, 47, 99. 24. Nicholls, A.; Sharp, K. A.; Honig, B. Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins 1991, 11, 281. 25. Nakamura, H. Roles of electrostatic interaction in proteins. Q. Rev. Biophys. 1996, 29, 1. 26. Makhatadze, G. I.; Privalov, P. L. Energetics of protein structure. Adv. Protein Chem. 1995, 47, 307. 27. Pauling, L.; Corey, R. B. The pleated sheet, a new layer configuration of polypeptide chains. Proc. Natl. Acad. Sci. U. S. A. 1951, 37, 251. 28. Hagler, A. T.; Huler, E.; Lifson, S. Energy functions for peptides and proteins. I. Derivation of a consistent force field including hydrogen-bond from amide crystals. J. Am. Chem. Soc. 1974, 96, 5319. 29. Hagler, A. T.; Lifson, S. Energy functions for peptides and proteins. II. The amide hydrogen bond and calculation of amide crystal properties. J. Am. Chem. Soc. 1974, 96, 5327. 30. Hamaker, H. C. The London-van der Waals attraction between spherical particles. Physica 1937, 4, 1058. 31. Levitt, M.; Gerstein, M.; Huang, E.; Subbiah, S.; Tsai, J. Protein folding: the endgame. Annu. Rev. Biochem. 1997, 66, 549. 32. Kuo, H.-T.; Fang, C.-J.; Tsai, H.-Y.; Yang, M.-F.; Chang, H.-C.; Liu, S.-L.; Kuo, L.- H.; Wang, W.-R.; Yang, P.-A.; Huang, S.-J.; Huang, S.-L.; Cheng, R. P. Effect of charged amino acid side chain length on lateral cross-strand interactions between carboxylate-containing residues and lysine analogues in a β-hairpin. Biochemistry 2013, 52, 9212. 33. Hobohm, U.; Scharf, M.; Schneider, R.; Sander, C. Selection of representative protein data sets. Protein Sci. 1992, 1, 409. 34. Hobohm, U.; Sander, C. Enlarged representative set of protein structures. Protein Sci. 1994, 3, 522. 35. Griep, S.; Hobohm, U. PDBselect 1992-2009 and PDBfilter-select. Nucleic Acids Res. 2010, 38, D318. 36. Chothia, C. Conformation of twisted β-pleated sheets in proteins. J. Mol. Biol. 1973, 75, 295. 37. Pauling, L.; Corey, R. B. The pleated sheet, a new layer configuration of polypeptide chains. Proc. Natl. Acad. Sci. U. S. A. 1951, 37, 251. 38. Syud, F. A.; Stanger, H. E.; Gellman, S. H. Interstrand side chain-side chain interactions in a designed β-hairpin: significance of both lateral and diagonal pairings. J. Am. Chem. Soc. 2001, 123, 8667. 39. Bartzokis, G.; Lu, P. H.; Mintz, J. Human brain myelination and amyloid β deposition in Alzheimer's disease. Alzheimers Dement. 2007, 3, 122. 40. Feany, M. B.; Bender, W. W. A Drosophila model of Parkinson's disease. Nature 2000, 404, 394. 41. Truant, R.; Atwal, R. S.; Desmond, C.; Munsie, L.; Tran, T. Huntington's disease: revisiting the aggregation hypothesis in polyglutamine neurodegenerative diseases. FEBS J. 2008, 275, 4252. 42. Kitamoto, T.; Tateishi, J.; Tashima, T.; Takeshita, I.; Barry, R. A.; Dearmond, S. J.; Prusiner, S. B. Amyloid plaques in Creutzfeldt-Jakob disease stain with prion protein antibodies. Ann. Neurol. 1986, 20, 204. 43. Chou, P. Y.; Fasman, G. D. β-Turns in proteins. J. Mol. Biol. 1977, 115, 135. 44. Venkatac.Cm. Stereochemical criteria for polypeptides and proteins. V. Conformation of a system of three linked peptide units. Biopolymers 1968, 6, 1425. 45. Wilmot, C. M.; Thornton, J. M. Analysis and prediction of the different types of β-turn in proteins. J. Mol. Biol. 1988, 203, 221. 46. Hutchinson, E. G.; Thornton, J. M. A revised set of potentials for β-turn formation in proteins. Protein Sci. 1994, 3, 2207. 47. Stanger, H. E.; Gellman, S. H. Rules for antiparallel β-sheet design: D-Pro-Gly is superior to L-Asn-Gly for β-hairpin nucleation. J. Am. Chem. Soc. 1998, 120, 4236. 48. Espinosa, J. F.; Syud, F. A.; Gellman, S. H. Analysis of the factors that stabilize a designed two-stranded antiparallel β=sheet. Protein Sci. 2002, 11, 1492. 49. Richardson, J. S. The anatomy and taxonomy of protein structure. Adv. Protein Chem. 1981, 34, 167. 50. Ramirez-Alvarado, M.; Kortemme, T.; Blanco, F. J.; Serrano, L. β-hairpin and β-sheet formation designed linear peptides. Bioorg. Med. Chem 1999, 7, 93. 51. Sibanda, B. L.; Blundell, T. L.; Thornton, J. M.; Conformations of β-hairpins in Protein Structures. A systematic classification with applications to modeling by homology, electron density fitting and protein engineering. J. Mol. Biol. 1989, 206, 759. 52. Kim, C. A.; Berg, J. M. Thermodynamic β-sheet propensities measured using a zinc-finger host peptide. Nature 1993, 362, 267. 53. Minor, D. L.; Kim, P. S. Measurement of β-sheet-forming propensities of amino acids. Nature 1994, 367, 660. 54. Dill, K. A. Dominant forces in protein folding. Biochemistry 1990, 29, 1773. 55. Chou, P. Y.; Fasman, G. D. Conformational parameters for amino acids in helical, β-sheet and random coilregions calculated from proteins. Biochemistry 1074, 13, 211. 56. Smith, C. K.; Withka, J. M.; Regan, L. A. A thermodynamic scale of the β-sheet forming tendencies of the amino acids. Biochemistry 1994, 33, 5510. 57. Tatko,C. D.; Waters, M. L. The geometry and efficacy of cation-π interactions in a diagonal position of a designed β-hairpin. Protein Sci. 2003, 12, 2443. 58. Tatko,C. D.; Waters, M. L. Comparison of C-H...π and hydrophobic interactions in a β-hairpin peptide: impacts on stability and specificity. J. Am. Chem. Soc. 2004, 126, 2028. 59. Searle, M. S.; Griffiths-Jones, S. R.; Skinner-Smith H. Energetics of weak interactions in a β-hairpin peptide: electrostatic and hydrophobic contributions to stability from lysine salt bridge. J. Am. Chem. Soc. 1999, 121, 11615. 60. Ramirez-Alvarado, M.; Blanco F. J.; Serrano L. Elongation of the Bh8 β-hairpin peptide: electrostatic interactions in β-hairpin formation and stability. Protein Sci. 2001, 10, 1381. 61. Kiehna, S. E.; Waters, M. L. Sequence dependence of β-hairpin structure: comparison of a salt bridge and an aromatic interaction. Protein Sci. 2003, 12, 2657. 62. Cheng, R. P.; Wang, W. R.; Girinath, P.; Yang, P. A.; Ahmad, R.; Li, J. H.; Hart, P.; Kokona, B.; Fairman, R.; Kilpatrick, C.; Argiros, A. Effect of glutamate side chain length on intrahelical glutamate-lysine ion pairing interactions. Biochemistry 2012, 51, 7157. 63. Hughes, R. M.; Benshoff, M. L. Effects of chain length and N-methylation on a cation-π interaction in a β-hairpin peptide. Chem. Eur. J. 2007, 13, 5753. 64. Strop, P.; Mayo, S. L. Contribution of surface salt bridge to protein stability. Biochemistry 2000, 39, 1251. 65. Andrew, C. D.; Panel, S.; Jones, G. R.; Doig, A. J. Stabilizing nonpolar/polar side chain interactions in the α-helix. Proteins 2001, 45, 449. 66. Olson, C. A.; Shi Z. S.; Kallenbach, N. R. Polar interactions with aromatic side chains in α-helical peptides: CH...O H-bonding and cation-π interactions. J. Am. Chem. Soc. 2001, 123, 6451. 67. Akke, M.; Forsen, S. Protein stability and electrostatic interactions between solvent exposed charged side chains. Proteins 1990, 8, 23. 68. Kuo, H.-T.; Fan, C.-J.; Tsai, H.-Y.; Yang, M.-F.; Chang, H.-C.; Liu, S.-L.; Kuo, L.-H.; Wang, W.-R.; Yang, P.-A.; Huang, S.-J., Huang, S.-L.; Cheng, R.-P. Effect of charged amino acid side chainlength on lateral cross-strand interactions between carboxylate-containing residues and lysine analogues in a β-hairpin. Biochemistry 2013, 52, 9212. 69. Volkmert-Engert, R.; Landgraf, C.; Schneider-Mergener, J. Charcoal surface-assisted catalysis of intramolecular disulfide bond formation in peptides. J. Pept. Res. 1998, 51, 365. 70. Fisk, J. D.; Powell, D. R.; Gellman, S. H. Control of hairpin formation via proline configuration in parallel β-sheet model system. J. Am. Chem. Soc. 2000, 122, 5443. 71. Atherton, E.; Fox, H.; Harkiss, D.; Logan, C. J.; Sheppard, R. C.; Williams, B. J. A mild procedure for solid phase peptide synthesis: use of fluorenylmethoxycarbonylamino-acids. J. Chem. Soc. Chem. Commun. 1978, 537. 72. Fields, G. B.; Noble, R. L.; Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. Int. J. Pept. Protein Res. 1990, 35, 161. 73. Bax, A.; Davis, D. G. Mlev-17-based two-dimensional homonuclear magnetization transfer spectroscopy. J. Magn. Reson. 1985, 65, 355. 74. Aue, W. P.; Bartholdi, E., Ernst; R. R. Two-dimensional spectroscopy. Application to nuclear magnetic resonance. J. Phys. Chem. 1976, 64, 2229. 75. Bothnerby, A. A.; Stephens, R. L.; Lee, J. M.; Warren, C. D.; Jeanloz, R. W. Structure determination of a tetrasaccharide-transient nuclear overhauser effects in the rotating frame. J. Am. Chem. Soc. 1984, 106, 811. 76. Wishart, D. S.; Sykes, B. D.; Richards, F. M. The chemical shift index: a fast and simple method for the assignment of the protein secondary structure through NMR spectroscopy. Biochemistry 1992, 31, 1647. 77. Wishart, D. S.; Sykes, B. D. Chemical shifts as a tool for structure determination. Method Enzymol. 1994, 239, 363 78. Dalgarno, D. C.; Levine, B. A.; Williams, R. J. P. Structural information from NMR secondary chemical shifts of peptide α C-H protons in proteins. Biosci. Rep. 1983, 3, 443. 79. Ciani, B. Jourdan, M.; Searle, M. S. Stabilization of β-hairpin peptides by salt bridges: role of preorganization in the energetic contribution of weak interactions. J. Am. Chem. Soc. 2003, 125, 9038. 80. RamirezAlvarado, M.; Blanco F. J.; Serrano L. De novo design and structural analysis of a model β-hairpin peptide system. Nat Struct Biol. 1996, 3, 604. 81. Kim, Y. M.; Prestegard, J. H. Measurement of vicinal couplings from cross peaks in COSY Spectra. J. Magn. Reson. 1989, 84, 9. 82. Syud, F. A.; Espinosa, J. F.; Gellman, S. H. NMR-based quantification of β-sheet populations in aqueous solution through use of reference peptides for the folded and unfolded states. J. Am. Chem. Soc. 1999, 121, 11577 83. DeAlba, E.; Rico, M.; Jimenez, M. A. Cross-strand side-chain interactions versus turn conformation β-hairpins. Protein Sci. 1997, 6, 2548. 84. Cockroft, S. L.; Hunter, C. A. Chemical double-mutant cycles: dissecting non-covalent interactions. Chem. Soc. Rev. 2007, 36, 172 85. Laughrey, Z. R.; Kiehna, S. E.; Riemen, A. J.; Waters, M. L. Carbonhydrate-π interaction: what are they worth? J. Am. Chem. Soc. 2008, 130, 14625. 86. Piotto, M.; Saudek, V.; Sklenar, V. Gradient-tailored excitation for single-quantum NMR spectroscopy of aqueous solutions. J. Biomol. NMR 1992, 2, 661. 87. Sklenar, V.; Piotto, M.; Leppik, R.; Saudek, V. Gradient-tailored water suppression for H-1-N-15 HSQC experiments optimized to retain full sensitivity. J. Magn. Reson. Ser. A 1993, 102, 241. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78101 | - |
| dc.description.abstract | β-Sheet是蛋白質中一種常見的二級結構，而股與股之間的作用力，例如：主鏈間的氫鍵或側鏈間的靜電作用力，都是可以使β-sheet結構穩定的主要作用力，然而，β-hairpin是反向平行β-sheet中最簡單的單元結構，因此為了探討帶電荷胺基酸側鏈長度對於β-sheet穩定度的關係，β-hairpin被設計作為實驗的模板。在β-hairpin中，股與股間位於正對或對角的胺基酸側鏈間的作用力都可以使得β-hairpin結構變得穩定，而對角位的胺基酸由於右手螺旋性質，使得在空間距離上變得接近，進而導致作用力的產生。在此研究中，我們探討了六種不同離子對的組合：Asp-Lys、Asp-Orn、Glu-Lys、Glu-Orn、Aad-Lys以及Aad-Orn，所有的胜肽都是利用固相合成法所合成，且利用高效能液化層析儀所純化，而2D-NMR的技術，包含了TOCSY、DQF-COSY以及ROESY則是被用來鑑定純化後的胜肽結構，β-hairpin的摺疊程度以及摺疊的自由能變化是由α質子的化學位移來判定。然而，實驗結果顯示出摺疊程度由大至小排列，依序為: HPDGluLys > HPDAadLys ≥ HPDGluOrn > HPDAadOrn > HPDAspOrn > HPDAspLys，此趨勢代表著離子對胺基酸側鏈愈長會使得β-hairpin結構的摺疊愈好、穩定度也愈高。 | zh_TW |
| dc.description.abstract | β-sheet is one of the common secondary structures in proteins. The β-sheet is mainly stabilized by backbone hydrogen bonds between adjacent strands and side chain interactions between amino acids on adjacent strands. To investigate how charged amino acid side chain length affects stability in β-sheets, a β-hairpin was studied as a model system, because β-hairpins are the simplest motif in antiparallel β-sheets. In a β-hairpin, lateral and diagonal cross-strand side chain-side chain interactions can stabilize the structure. The diagonal sites are spatially closer due to the right-handed twist. In this study, six diagonal cross-strand ion pairs were investigated: Asp-Lys, Asp-Orn, Glu-Lys, Glu-Orn, Aad-Lys, and Aad-Orn. All peptides were synthesized by solid phase peptide synthesis using Fmoc-based chemistry and were purified by HPLC to at least 95% purity. After purification, the structures of the peptides were analyzed by 2D-NMR spectroscopy, acquiring TOCSY, DQF-COSY, and ROESY spectra. The β-hairpin population and folding free energy were determined from the chemical shifts of the α-protons. The results showed the fraction folded followed the trend HPDGluLys > HPDAadLys ≥ HPDGluOrn > HPDAadOrn > HPDAspOrn > HPDAspLys. This trend revealed that combinations with longer side chains gave higher hairpin stability. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T14:42:16Z (GMT). No. of bitstreams: 1 ntu-105-R03223210-1.pdf: 4396115 bytes, checksum: d51a4a2993bd500ee8c5778547c74efe (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | Table of Contents
口試委員會審定書 (i) 謝誌 (iii) 中文摘要 (vii) Abstract (ix) Table of Contents (xi) List of Figures (xiv) List of Tables (xvii) List of Schemes (xix) Abbreviation (xx) Chapter 1 Introduction (1) 1.1 Proteins (3) 1.2 Protein Structures (5) 1.3 Driving Forces for Protein Folding (7) Electrostatic Interactions (8) Hydrophobic Effect (9) Hydrogen Bonding (9) Van der Waals Interactions (10) 1.4 Thesis Overview (10) 1.5 Reference (11) Chapter 2 Effect of Charged Amino Acid Side Chain Length in Diagonal Ion Pairing Interactions on β-Hairpin Stability (15) 2.1 Introduction (17) β-Sheet (17) β-Turns (18) β-Hairpins (20) β-Sheet Propensity (21) Cross-Strand Interactions (21) Effect of Charged Residue Side Chain Length (22) 2.2 Results and Discussion (24) Peptide Design (24) Peptide Synthesis and Purification (26) NMR Spectroscopy (28) β-Hairpin Structure Characterization (28) Hairpin Stability (48) Double Mutant Cycle and Ion Pairing Interaction (51) 2.3 Conclusion (54) 2.4 Acknowledgement (54) 2.5 Experimental Section (55) General Material and Methods (55) Peptide Synthesis (56) NMR Sample Preparation and Measurement (80) Chemical Shift Deviation (80) 3JNHα Coupling Constant (81) NOE Signal Integration for Distance Determination (81) Fraction Folded and Gfold (82) Double Mutant Cycle (82) 2.6 References (83) | |
| dc.language.iso | en | |
| dc.title | 對角帶電荷胺基酸側鏈長度對β-Hairpin穩定度影響 | zh_TW |
| dc.title | Effect of Charged Amino Acid Side Chain Length in Diagonal Ion Pairing Interactions on β-Hairpin Stability | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳佩燁,黃人則 | |
| dc.subject.keyword | β-摺板,β-hairpin,對角,離子對作用力, | zh_TW |
| dc.subject.keyword | β-Sheet,β-Hairpin,Diagonal,Ion-pairing interaction, | en |
| dc.relation.page | 99 | |
| dc.identifier.doi | 10.6342/NTU201602451 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-08-19 | |
| dc.contributor.author-college | 理學院 | zh_TW |
| dc.contributor.author-dept | 化學研究所 | zh_TW |
| 顯示於系所單位： | 化學系 | |
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