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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 詹迺立(Nei-Li Chan) | |
| dc.contributor.author | Chun-Yi Yeh | en |
| dc.contributor.author | 葉君毅 | zh_TW |
| dc.date.accessioned | 2021-06-15T12:55:16Z | - |
| dc.date.available | 2021-08-26 | |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-07-15 | |
| dc.identifier.citation | 1. Ahn, T., Bae, C.-S. and Yun, C.-H. (2014). 'Affinity purification of recombinant human cytochrome P450s 3A4 and 1A2 using mixed micelle systems.' Protein Expression and Purification 101: 37-41.
2. Amano, H., Ito, Y., Eshima, K., Kato, S., Ogawa, F., Hosono, K., Oba, K., Tamaki, H., Sakagami, H., Shibuya, M., Narumiya, S. and Majima, M. (2015). 'Thromboxane A2 induces blood flow recovery via platelet adhesion to ischaemic regions.' Cardiovasc Res 107(4): 509-521. 3. Antman, E. M., DeMets, D. and Loscalzo, J. (2005). 'Cyclooxygenase inhibition and cardiovascular risk.' Circulation 112(5): 759-770. 4. Barnes, H. J., Arlotto, M. P. and Waterman, M. R. (1991). 'Expression and enzymatic activity of recombinant cytochrome P450 17 alpha-hydroxylase in Escherichia coli.' Proc Natl Acad Sci U S A 88(13): 5597-5601. 5. Baylon, J. L., Lenov, I. L., Sligar, S. G. and Tajkhorshid, E. (2013). 'Characterizing the membrane-bound state of cytochrome P450 3A4: structure, depth of insertion, and orientation.' J Am Chem Soc 135(23): 8542-8551. 6. Cathcart, M. C., Gately, K., Cummins, R., Kay, E., O'Byrne, K. J. and Pidgeon, G. P. (2011). 'Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer.' Mol Cancer 10: 25. 7. Cathcart, M. C., Reynolds, J. V., O'Byrne, K. J. and Pidgeon, G. P. (2010). 'The role of prostacyclin synthase and thromboxane synthase signaling in the development and progression of cancer.' Biochim Biophys Acta 1805(2): 153-166. 8. Chen, Z., Wang, L. H. and Schelvis, J. P. (2003). 'Resonance Raman investigation of the interaction of thromboxane synthase with substrate analogues.' Biochemistry 42(9): 2542-2551. 9. Chiang, C. W., Yeh, H. C., Wang, L. H. and Chan, N. L. (2006). 'Crystal structure of the human prostacyclin synthase.' J Mol Biol 364(3): 266-274. 10. Childers, W. K. and Harrelson, J. P. (2014). 'Allosteric modulation of substrate motion in cytochrome P450 3A4-mediated xylene oxidation.' Biochemistry 53(6): 1018-1028. 11. Cho, M. J. and Allen, M. A. (1978). 'Chemical stability of prostacyclin (PGI2) in aqueous solutions.' Prostaglandins 15(6): 943-954. 12. Cho, S. A., Rohn-Glowacki, K. J., Jarrar, Y. B., Yi, M., Kim, W. Y., Shin, J. G. and Lee, S. J. (2015). 'Analysis of genetic polymorphism and biochemical characterization of a functionally decreased variant in prostacyclin synthase gene (CYP8A1) in humans.' Arch Biochem Biophys 569: 10-18. 13. Dapkunas, J., Sazonovas, A. and Japertas, P. (2009). 'Probabilistic prediction of the human CYP3A4 and CYP2D6 metabolism sites.' Chem Biodivers 6(11): 2101-2106. 14. Das, A., Varma, S. S., Mularczyk, C. and Meling, D. D. (2014). 'Functional investigations of thromboxane synthase (CYP5A1) in lipid bilayers of nanodiscs.' Chembiochem 15(6): 892-899. 15. Denisov, I. G., Makris, T. M., Sligar, S. G. and Schlichting, I. (2005). 'Structure and chemistry of cytochrome P450.' Chem Rev 105(6): 2253-2277. 16. Diczfalusy, U., Falardeau, P. and Hammarstrom, S. (1977). 'Conversion of prostaglandin endoperoxides to C17-hydroxy acids catalyzed by human platelet thromboxane synthase.' FEBS Lett 84(2): 271-274. 17. Ding, X. Z., Hennig, R. and Adrian, T. E. (2003). 'Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer.' Mol Cancer 2: 10. 18. Dong, D. and Wu, B. (2012). 'Substrate selectivity of drug-metabolizing cytochrome P450s predicted from crystal structures and in silico modeling.' Drug Metab Rev 44(1): 1-17. 19. Egan, K. and FitzGerald, G. A. (2006). 'Eicosanoids and the vascular endothelium.' Handb Exp Pharmacol(176 Pt 1): 189-211. 20. Eisinger, A. L., Prescott, S. M., Jones, D. A. and Stafforini, D. M. (2007). 'The role of cyclooxygenase-2 and prostaglandins in colon cancer.' Prostaglandins Other Lipid Mediat 82(1-4): 147-154. 21. Ekambaram, P., Lambiv, W., Cazzolli, R., Ashton, A. W. and Honn, K. V. (2011). 'The thromboxane synthase and receptor signaling pathway in cancer: an emerging paradigm in cancer progression and metastasis.' Cancer Metastasis Rev 30(3-4): 397-408. 22. Funk, C. D. (2001). 'Prostaglandins and leukotrienes: advances in eicosanoid biology.' Science 294(5548): 1871-1875. 23. Hammarstrom, S. and Falardeau, P. (1977). 'Resolution of prostaglandin endoperoxide synthase and thromboxane synthase of human platelets.' Proc Natl Acad Sci U S A 74(9): 3691-3695. 24. Hasemann, C. A., Kurumbail, R. G., Boddupalli, S. S., Peterson, J. A. and Deisenhofer, J. (1995). 'Structure and function of cytochromes P450: a comparative analysis of three crystal structures.' Structure 3(1): 41-62. 25. Hecker, M. and Ullrich, V. (1989). 'On the mechanism of prostacyclin and thromboxane A2 biosynthesis.' J Biol Chem 264(1): 141-150. 26. Hsu, P. Y., Tsai, A. L. and Wang, L. H. (2000). 'Identification of thromboxane synthase amino acid residues involved in heme-propionate binding.' Arch Biochem Biophys 383(1): 119-127. 27. Hsu, P.-Y. and Wang, L.-H. (2003). 'Protein engineering of thromboxane synthase: conversion of membrane-bound to soluble form.' Archives of Biochemistry and Biophysics 416(1): 38-46. 28. Huang, R. Y., Chu, Y. L., Huang, Q. C., Chen, X. M., Jiang, Z. B., Zhang, X. and Zeng, X. (2014). '18beta-Glycyrrhetinic acid suppresses cell proliferation through inhibiting thromboxane synthase in non-small cell lung cancer.' PLoS One 9(4): e93690. 29. Jiang, W. and Ghosh, D. (2012). 'Motion and flexibility in human cytochrome p450 aromatase.' PLoS One 7(2): e32565. 30. Kajita, S., Ruebel, K. H., Casey, M. B., Nakamura, N. and Lloyd, R. V. (2005). 'Role of COX-2, thromboxane A2 synthase, and prostaglandin I2 synthase in papillary thyroid carcinoma growth.' Mod Pathol 18(2): 221-227. 31. Kim, S. R., Jung, Y. H., Park, H. J., Kim, M. K., Jeong, J. W., Jang, H. O., Yun, I., Bae, S. K. and Bae, M. K. (2012). 'Upregulation of thromboxane synthase mediates visfatin-induced interleukin-8 expression and angiogenic activity in endothelial cells.' Biochem Biophys Res Commun 418(4): 662-668. 32. Kontogiorgis, C. and Hadjipavlou-Litina, D. (2010). 'Thromboxane synthase inhibitors and thromboxane A2 receptor antagonists: a quantitative structure activity relationships (QSARs) analysis.' Curr Med Chem 17(28): 3162-3214. 33. Lee, S. and Kim, D. (2010). 'Cytochrome P450 networks in chemical space.' Arch Pharm Res 33(9): 1361-1374. 34. Li, Y. C., Chiang, C. W., Yeh, H. C., Hsu, P. Y., Whitby, F. G., Wang, L. H. and Chan, N. L. (2008). 'Structures of prostacyclin synthase and its complexes with substrate analog and inhibitor reveal a ligand-specific heme conformation change.' J Biol Chem 283(5): 2917-2926. 35. Meling, D. D., Zelasko, S., Kambalyal, A., Roy, J. and Das, A. (2015). 'Functional role of the conserved i-helix residue I346 in CYP5A1-Nanodiscs.' Biophys Chem 200-201: 34-40. 36. Mestres, J. (2005). 'Structure conservation in cytochromes P450.' Proteins 58(3): 596-609. 37. Minamino, T., Ito, Y., Ohkubo, H., Shimuzu, Y., Kojo, K., Nishizwa, N., Amano, H., Narumiya, S., Koizumi, W. and Majima, M. (2015). 'Adhesion of platelets through thromboxane A(2) receptor signaling facilitates liver repair during acute chemical-induced hepatotoxicity.' Life Sci 132: 85-92. 38. Miyata, A., Yokoyama, C., Ihara, H., Bandoh, S., Takeda, O., Takahashi, E. and Tanabe, T. (1994). 'Characterization of the human gene (TBXAS1) encoding thromboxane synthase.' Eur J Biochem 224(2): 273-279. 39. Moncada, S. and Vane, J. R. (1978). 'Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2, and prostacyclin.' Pharmacol Rev 30(3): 293-331. 40. Moussa, O., Yordy, J. S., Abol-Enein, H., Sinha, D., Bissada, N. K., Halushka, P. V., Ghoneim, M. A. and Watson, D. K. (2005). 'Prognostic and functional significance of thromboxane synthase gene overexpression in invasive bladder cancer.' Cancer Res 65(24): 11581-11587. 41. Murray, R. and FitzGerald, G. A. (1989). 'Regulation of thromboxane receptor activation in human platelets.' Proc Natl Acad Sci U S A 86(1): 124-128. 42. Muzaffar, S., Shukla, N., Massey, Y., Angelini, G. D. and Jeremy, J. Y. (2011). 'NADPH oxidase 1 mediates upregulation of thromboxane A2 synthase in human vascular smooth muscle cells: inhibition with iloprost.' Eur J Pharmacol 658(2-3): 187-192. 43. Nakahata, N. (2008). 'Thromboxane A2: physiology/pathophysiology, cellular signal transduction and pharmacology.' Pharmacol Ther 118(1): 18-35. 44. Neve, E. P. and Ingelman-Sundberg, M. (2008). 'Intracellular transport and localization of microsomal cytochrome P450.' Anal Bioanal Chem 392(6): 1075-1084. 45. Nie, D., Lamberti, M., Zacharek, A., Li, L., Szekeres, K., Tang, K., Chen, Y. and Honn, K. V. (2000). 'Thromboxane A(2) regulation of endothelial cell migration, angiogenesis, and tumor metastasis.' Biochem Biophys Res Commun 267(1): 245-251. 46. Ortiz de Montellano, P. R. and Nelson, S. D. (2011). 'Rearrangement reactions catalyzed by cytochrome P450s.' Arch Biochem Biophys 507(1): 95-110. 47. Pilgrim, J. L., Gerostamoulos, D. and Drummer, O. H. (2011). 'Review: Pharmacogenetic aspects of the effect of cytochrome P450 polymorphisms on serotonergic drug metabolism, response, interactions, and adverse effects.' Forensic Sci Med Pathol 7(2): 162-184. 48. Poulos, T. L. (2005). 'Structural biology of heme monooxygenases.' Biochem Biophys Res Commun 338(1): 337-345. 49. Ratti, S., Quarato, P., Casagrande, C., Fumagalli, R. and Corsini, A. (1998). 'Picotamide, an antithromboxane agent, inhibits the migration and proliferation of arterial myocytes.' European Journal of Pharmacology 355(1): 77–83. 50. Rittle, J. and Green, M. T. (2010). 'Cytochrome P450 compound I: capture, characterization, and C-H bond activation kinetics.' Science 330(6006): 933-937. 51. Ruan, K. H., Wu, J. and Wang, L. H. (2005). 'Solution structure of a common substrate mimetic of cyclooxygenase-downstream synthases bound to an engineered thromboxane A2 synthase using a high-resolution NMR technique.' Arch Biochem Biophys 444(2): 165-173. 52. Saito, S., Tsuda, H. and Michimata, T. (2002). 'Prostaglandin D2 and reproduction.' Am J Reprod Immunol 47(5): 295-302. 53. Scott, E. E. and Halpert, J. R. (2005). 'Structures of cytochrome P450 3A4.' Trends Biochem Sci 30(1): 5-7. 54. Scow, D. T., Robert, S., Nolte, D. O. and Allen, F. (1999). 'Medical treatment for balding in men.' Am Fam Physician 59(8): 2189-2194. 55. Sevrioukova, I. F. and Poulos, T. L. (2012). 'Structural and mechanistic insights into the interaction of cytochrome P4503A4 with bromoergocryptine, a type I ligand.' J Biol Chem 287(5): 3510-3517. 56. Sharma, I., Dhaliwal, L. K., Saha, S. C., Sangwan, S. and Dhawan, V. (2010). 'Role of 8-iso-prostaglandin F2alpha and 25-hydroxycholesterol in the pathophysiology of endometriosis.' Fertil Steril 94(1): 63-70. 57. Shityakov, S., Puskas, I., Roewer, N., Forster, C. and Broscheit, J. (2014). 'Three-dimensional quantitative structure-activity relationship and docking studies in a series of anthocyanin derivatives as cytochrome P450 3A4 inhibitors.' Adv Appl Bioinform Chem 7: 11-21. 58. Smyth, E. M. (2010). 'Thromboxane and the thromboxane receptor in cardiovascular disease.' Clin Lipidol 5(2): 209-219. 59. Son, D. J., Akiba, S., Hong, J. T., Yun, Y. P., Hwang, S. Y., Park, Y. H. and Lee, S. E. (2014). 'Piperine inhibits the activities of platelet cytosolic phospholipase A2 and thromboxane A2 synthase without affecting cyclooxygenase-1 activity: different mechanisms of action are involved in the inhibition of platelet aggregation and macrophage inflammatory response.' Nutrients 6(8): 3336-3352. 60. Ullrich, V. B., R. (1994). 'Prostacyclin and Thromboxane Synthase New Aspects of Hemethiolate Catalysis.'. 61. Waltenberger, B., Wiechmann, K., Bauer, J., Markt, P., Noha, S. M., Wolber, G., Rollinger, J. M., Werz, O., Schuster, D. and Stuppner, H. (2011). 'Pharmacophore modeling and virtual screening for novel acidic inhibitors of microsomal prostaglandin E(2) synthase-1 (mPGES-1).' J Med Chem 54(9): 3163-3174. 62. Wang, L. H. and Kulmacz, R. J. (2002). 'Thromboxane synthase: structure and function of protein and gene.' Prostaglandins Other Lipid Mediat 68-69: 409-422. 63. Wang, L. H., Tsai, A. L. and Hsu, P. Y. (2001). 'Substrate binding is the rate-limiting step in thromboxane synthase catalysis.' J Biol Chem 276(18): 14737-14743. 64. WHO fact sheet. (2014). 'The top 10 causes of death. ' http://www.who.int/mediacentre/factsheets/fs310/en/ 65. Williams, P. A., Cosme, J., Vinkovic, D. M., Ward, A., Angove, H. C., Day, P. J., Vonrhein, C., Tickle, I. J. and Jhoti, H. (2004). 'Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone.' Science 305(5684): 683-686. 66. Yanai, T. K. and Mori, S. (2008). 'Density functional studies on thromboxane biosynthesis: mechanism and role of the heme-thiolate system.' Chem Asian J 3(11): 1900-1911. 67. Zhou, Z., Sun, C., Tilley, S. L. and Mustafa, S. J. (2015). 'Mechanisms underlying uridine adenosine tetraphosphate-induced vascular contraction in mouse aorta: Role of thromboxane and purinergic receptors.' Vascul Pharmacol 73: 78-85. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50734 | - |
| dc.description.abstract | 世界衛生組織之統計顯示，世界前十大死因中，心血管相關疾病就佔了三項，因此若能有效的治療與控制心血管疾病，勢必是人類的一大福音。心血管疾病與體內前列腺素H2 (prostaglandin H2, PGH2) 及其下游產物 (prostanoids) 的含量與生物活性是息息相關的，其中血栓素合成酶(thromboxane A2 synthase, TXAS) 和前列環素合成酶(prostacyclin synthase, PGIS) 是調控心血管功能的要角。血栓素合成酶可以把前列腺素H2催化為血栓素(thromboxane A2, TXA2)，而前列環素合成酶則可以把前列腺素H2催化為前列環素(prostacyclin, PGI2)，催化機制是利用血基質上的鐵離子辨認並與前列腺素H2之內過氧化基團(endoperoxide) 中不同位置的氧結合(血栓素合成酶辨識C9-O；前列環素合成酶辨識C11-O)，再經由血基質引發的O–O鍵裂解，合成不同的產物。血栓素是個非常有效的血管收縮劑，並可誘發血小板的聚集與釋放，而形成血栓；前列環素則恰好與之拮抗，可使血管舒張及抑制血小板凝集。本研究希望可以藉由解析此兩種酵素的晶體結構，而了解二者催化專一性的結構基礎。
我們先使用 E. coli 大量表達血栓素合成酶和前列環素合成酶，並使用液相層析法進行蛋白純化，接著利用受質前列腺素H2 的類似物U51605 與兩種酵素結合，進行複合體的結晶嘗試，目前已順利解出人類前列環素合成酶與U51605 形成的複合體結構，發現U51605 結合可改變血基質之丙酸基(propionate groups) 與酵素活性中心附近鹼性胺基酸的交互作用，先前本實驗室亦曾在斑馬魚前列環素合成酶的結構中觀察到此種構形變化，推測應與酵素催化電子傳遞反應與O–O 鍵裂解的效率有關。目前也順利發現血栓素合成酶的結晶條件，並積極進行血栓素合成酶與U51605、U44069 等受質類似物形成之複合體的結構解析，期待藉由比較二者活性中心與受質結合的異同，輔助血栓素合成酶專一性抑制劑的開發。 | zh_TW |
| dc.description.abstract | Statistics conducted by the World Health Organization reveals that cardiovascular-related diseases claim three spots among the top 10 causes of death. Therefore, it is crucial to develop new diagnostic tools and effective treatments for these diseases. Previous studies provide a strong indication that the production and biological activities of prostaglandin H2 (PGH2) and its downstream prostanoids are linked closely to the cardiovascular functions. Using PGH2 as the common substrate, thromboxane A2 synthase (TXAS) and prostacyclin synthase (PGIS) catalyze respectively the production of thromboxane A2 (TXA2), a potent inducer of vasoconstriction and platelet aggregation, and prostacyclin (PGI2), a vasodilator and inhibitor of thrombosis. How mechanistically does these two enzymes use the same substrate but generate different products with completely opposite biological activities? Spectroscopic studies suggested that TXAS interacts with the C-9 oxygen of PGH2 using its ferric heme, whereas PGIS bind to the C-11 oxygen by its heme iron. The goal of this work is to provide a structural understanding on the strict catalytic stereo-specificity of these two synthases.
To this end, I have successfully determined the crystal structure of PGIS in complex with the substrate analog U51605. This result demonstrates a stereo-specific substrate binding and suggest structural features of the enzyme that may facilitate isomerization to produce PGI2. In addition, by employing a new purification protocol, I have prepared large amount of structurally and functionally intact TXAS and obtained diffracting crystals of this important enzyme. It is hopeful that the crystal structure of TXAS will be determined by X-ray crystallography in the near future to provide new insights into its catalytic mechanism. Moreover, with the crystal structures of both TXAS and PGIS available, it is possible to design small molecule inhibitors that specifically inhibit TXAS but not PGIS, for treating cardiovascular diseases. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T12:55:16Z (GMT). No. of bitstreams: 1 ntu-105-R03442003-1.pdf: 29012423 bytes, checksum: 1701cf1a46f4f323d3023f4733c11a35 (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 口試委員會論文審定書......................................i
謝誌.....................................................ii 中文摘要.................................................vi 英文摘要...............................................viii 目錄......................................................x 圖目錄.................................................xiii 表目錄...................................................xv 縮寫表..................................................xvi 一、 引言..................................................1 1-1 前言.................................................1 1-2 細胞色素P450 (Cytochrome P450).......................2 1-3 細胞色素P450蛋白結構之特色...........................3 1-4 Prostanoids之合成路徑與組成成員......................5 1-5 血栓素合成酶 (Thromboxane A2 Synthase, TXAS) 之催化機制...5 1-6 前列環素合成酶 (Prostacyclin Synthase, PGIS) 之催化機制...6 1-7 血栓素合成酶與前列環素合成酶在體內之拮抗關係…….....7 1-8 前列環素合成酶與其催化中心之結構研究........……..….8 1-9 目前治療心血管相關疾病之藥物與研發新藥的困境.........9 1-10 研究動機與目的...................................…10 二、 材料與方法...........................................11 2-1 實驗材料............................................11 2-2 實驗方法............................................11 2-2-1 人類血栓素合成酶及人類前列環素合成酶之小量表現測試方法....11 2-2-2 人類血栓素合成酶及人類前列環素合成酶之純化......13 2-2-2-1 人類血栓素合成酶及人類前列環素合成酶之大量表現破菌與萃取.13 2-2-2-2 鎳離子親和性管柱............................14 2-2-2-3 脫鹽管柱.........................................15 2-2-2-4 陽離子交換管柱..............................15 2-2-2-5 分子篩膠體過濾管柱..........................16 2-2-3 人類血栓素合成酶及人類前列環素合成酶之定量….......16 2-2-4 人類血栓素合成酶及人類前列環素合成酶與受質類似物的交互作用...16 2-2-5 人類血栓素合成酶及人類前列環素合成酶之結晶......17 2-2-6 人類血栓素合成酶及人類前列環素合成酶晶體之X-ray繞射...18 2-2-6-1 晶體之X-ray繞射的資料收集.........................18 2-2-6-2 晶體之結構解析....................................19 三、 結果.................................................20 3-1 人類血栓素合成酶 (human Thromboxane A2 Synthase, hTXAS)...20 3-1-1 人類血栓素合成酶之小量表現測試......................20 3-1-2 人類血栓素合成酶之純化..............................21 3-1-3 人類血栓素合成酶與受質類似物之交互作用..............22 3-1-4 人類血栓素合成酶之結晶與繞射點數據收集..............23 3-1-5 人類血栓素合成酶之結構解析..........................24 3-2 人類前列環素合成酶 (human Prostacyclin Synthase, hPGIS)...25 3-2-1 人類前列環素合成酶之小量表現測試....................25 3-2-2 人類前列環素合成酶之純化............................25 3-2-3 人類前列環素合成酶與受質類似物之交互作用............26 3-2-4 人類前列環素合成酶之結晶與繞射點數據收集............26 3-2-5 人類前列環素合成酶與U51605形成之複合體的結構解析....27 3-2-5-1 人類前列環素合成酶與U51605結合之結構決定與優化...27 3-2-5-2 人類前列環素合成酶與U51605結合之整體構造.........28 3-2-5-3 人類前列環素合成酶與U51605結合之活性中心…….....29 3-2-5-4 人類前列環素合成酶與U51605結合和已解出晶體結構之同源蛋白比較...30 3-2-5-5 人類前列環素合成酶催化受質活性之重要胺基酸…......32 四、 討論.................................................33 4-1 人類血栓素合成酶目前所解決之問題與觸及之瓶頸…...….33 4-2 人類血栓素合成酶和人類前列環素合成酶與受質類似物交互作用之比較...35 4-3 人類前列環素合成酶負責催化功能之重要胺基酸.........36 五、 圖...................................................38 六、 表...................................................74 七、 參考文獻………...........................……….....76 八、附錄……............................................84 | |
| dc.language.iso | zh-TW | |
| dc.subject | 血栓素合成?(CYP5A1) | zh_TW |
| dc.subject | 前列環素合成?(CYP8A1) | zh_TW |
| dc.subject | 細胞色素P450 | zh_TW |
| dc.subject | 心血管疾病 | zh_TW |
| dc.subject | 蛋白質結晶 | zh_TW |
| dc.subject | X-ray 繞射分析 | zh_TW |
| dc.subject | X-ray 繞射分析 | zh_TW |
| dc.subject | 蛋白質結晶 | zh_TW |
| dc.subject | 心血管疾病 | zh_TW |
| dc.subject | 血栓素合成?(CYP5A1) | zh_TW |
| dc.subject | 細胞色素P450 | zh_TW |
| dc.subject | 前列環素合成?(CYP8A1) | zh_TW |
| dc.subject | X-ray diffraction | en |
| dc.subject | thromboxane A2 synthase (TXAS | en |
| dc.subject | CYP5A1) | en |
| dc.subject | prostacyclin synthase (PGIS | en |
| dc.subject | CYP8A1) | en |
| dc.subject | cytochrome P450 | en |
| dc.subject | cardiovascular vessel disease | en |
| dc.subject | protein crystallography | en |
| dc.subject | X-ray diffraction | en |
| dc.subject | thromboxane A2 synthase (TXAS | en |
| dc.subject | CYP5A1) | en |
| dc.subject | prostacyclin synthase (PGIS | en |
| dc.subject | CYP8A1) | en |
| dc.subject | cytochrome P450 | en |
| dc.subject | cardiovascular vessel disease | en |
| dc.subject | protein crystallography | en |
| dc.title | 血栓素合成酶與前列環素合成酶之結構分析 | zh_TW |
| dc.title | Structural Analysis of Thromboxane A2 Synthase and Prostacyclin Synthase | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 曾秀如(Shiou-Ru Tzeng),徐駿森(Chun-Hua Hsu) | |
| dc.subject.keyword | 血栓素合成?(CYP5A1),前列環素合成?(CYP8A1),細胞色素P450,心血管疾病,蛋白質結晶,X-ray 繞射分析, | zh_TW |
| dc.subject.keyword | thromboxane A2 synthase (TXAS, CYP5A1),prostacyclin synthase (PGIS, CYP8A1),cytochrome P450,cardiovascular vessel disease,protein crystallography,X-ray diffraction, | en |
| dc.relation.page | 87 | |
| dc.identifier.doi | 10.6342/NTU201600549 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-07-18 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-105-1.pdf 未授權公開取用 | 28.33 MB | Adobe PDF |
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