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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 梁博煌 | |
| dc.contributor.author | Chia-Hsiang Lo | en |
| dc.contributor.author | 羅嘉翔 | zh_TW |
| dc.date.accessioned | 2021-06-13T00:22:09Z | - |
| dc.date.available | 2007-07-31 | |
| dc.date.copyright | 2007-07-31 | |
| dc.date.issued | 2007 | |
| dc.date.submitted | 2007-07-27 | |
| dc.identifier.citation | (1) Poulter C. D. & Rilling, H. C. (1981) Prenyl transferase and isomerase. Biosynthesis of isoprenoid compounds (Spurgeon, SL, R., ed.) 1, 161-224.
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(1999) Chain-length determination mechanism of isoprenyl diphosphate synthases and implications for molecular evolution. Trends Biochem Sci 24, 445-51. (10) Shimizu, N., Koyama, T., and Ogura, K. (1998) Molecular cloning, expression, and purification of undecaprenyl diphosphate synthase. No sequence similarity between E- and Z-prenyl diphosphate synthases. J Biol Chem 273, 19476-81. (11) Apfel, C. M., Takacs, B., Fountoulakis, M., Stieger, M., and Keck, W. (1999) Use of genomics to identify bacterial undecaprenyl pyrophosphate synthetase: cloning, expression, and characterization of the essential uppS gene. J Bacteriol 181, 483-92. (12) Fujihashi, M., Zhang, Y. W., Higuchi, Y., Li, X. Y., Koyama, T., and Miki, K. (2001) Crystal structure of cis-prenyl chain elongating enzyme, undecaprenyl diphosphate synthase. Proc Natl Acad Sci U S A 98, 4337-42. (13) Ko, T. P., Chen, Y. K., Robinson, H., Tsai, P. C., Gao, Y. G., Chen, A. P., Wang, A. H., and Liang, P. H. (2001) Mechanism of product chain length determination and the role of a flexible loop in Escherichia coli undecaprenyl-pyrophosphate synthase catalysis. J Biol Chem 276, 47474-82. (14) Tarshis, L. C., Yan, M., Poulter, C. D., and Sacchettini, J. C. (1994) Crystal structure of recombinant farnesyl diphosphate synthase at 2.6-A resolution. Biochemistry 33, 10871-7. (15) Guo, R. T., Kuo, C. J., Chou, C. C., Ko, T. P., Shr, H. L., Liang, P. H., and Wang, A. H. (2004) Crystal structure of octaprenyl pyrophosphate synthase from hyperthermophilic Thermotoga maritima and mechanism of product chain length determination. J Biol Chem 279, 4903-12. (16) Hosfield, D. J., Zhang, Y., Dougan, D. R., Broun, A., Tari, L. W., Swanson, R. V., and Finn, J. (2004) Structural basis for bisphosphonate-mediated inhibition of isoprenoid biosynthesis. J Biol Chem 279, 8526-9. (17) Sun, H. Y., Ko, T. P., Kuo, C. J., Guo, R. T., Chou, C. C., Liang, P. H., and Wang, A. H. (2005) Homodimeric hexaprenyl pyrophosphate synthase from the thermoacidophilic crenarchaeon Sulfolobus solfataricus displays asymmetric subunit structures. J Bacteriol 187, 8137-48. (18) Chang, T. H., Guo, R. T., Ko, T. P., Wang, A. H., and Liang, P. H. (2006) Crystal Structure of Type-III Geranylgeranyl Pyrophosphate Synthase from Saccharomyces cerevisiae and the Mechanism of Product Chain Length Determination. J Biol Chem 281, 14991-5000. (19) Chang, S. Y., Ko, T. P., Chen, A. P., Wang, A. H., and Liang, P. H. (2004) Substrate binding mode and reaction mechanism of undecaprenyl pyrophosphate synthase deduced from crystallographic studies. Protein Sci 13, 971-8. (20) Chang, S. Y., Ko, T. P., Liang, P. H., and Wang, A. H. (2003) Catalytic mechanism revealed by the crystal structure of undecaprenyl pyrophosphate synthase in complex with sulfate, magnesium, and Triton. J. Biol. Chem. 278, 29298-29307. (21) Guo, R. T., Ko, T. P., Chen, A. P., Kuo, C. J., Wang, A. H., and Liang, P. H. (2005) Crystal structures of undecaprenyl pyrophosphate synthase in complex with magnesium, isopentenyl pyrophosphate, and farnesyl thiopyrophosphate: roles of the metal ion and conserved residues in catalysis. J Biol Chem 280, 20762-74. (22) Chen, A., Kroon, P. A., and Poulter, C. D. (1994) Isoprenyl diphosphate synthases: protein sequence comparisons, a phylogenetic tree, and predictions of secondary structure. Protein Sci 3, 600-7. (23) Jiang, Y., Proteau, P., Poulter, D., and Ferro-Novick, S. (1995) BTS1 encodes a geranylgeranyl diphosphate synthase in Saccharomyces cerevisiae. J Biol Chem 270, 21793-9. (24) Kuzuguchi, T., Morita, Y., Sagami, I., Sagami, H., and Ogura, K. (1999) Human geranylgeranyl diphosphate synthase. cDNA cloning and expression. J Biol Chem 274, 5888-94. (25) Tarshis, L. C., Proteau, P. J., Kellogg, B. A., Sacchettini, J. C., and Poulter, C. D. (1996) Regulation of product chain length by isoprenyl diphosphate synthases. Proc Natl Acad Sci U S A 93, 15018-23. (26) Ohnuma, S., Nakazawa, T., Hemmi, H., Hallberg, A. M., Koyama, T., Ogura, K., and Nishino, T. (1996) Conversion from farnesyl diphosphate synthase to geranylgeranyl diphosphate synthase by random chemical mutagenesis. J Biol Chem 271, 10087-95. (27) Ohnuma, S., Narita, K., Nakazawa, T., Ishida, C., Takeuchi, Y., Ohto, C., and Nishino, T. (1996) A role of the amino acid residue located on the fifth position before the first aspartate-rich motif of farnesyl diphosphate synthase on determination of the final product. J Biol Chem 271, 30748-54. (28) Ohnuma, S., Hirooka, K., Hemmi, H., Ishida, C., Ohto, C., and Nishino, T. (1996) Conversion of product specificity of archaebacterial geranylgeranyl-diphosphate synthase. Identification of essential amino acid residues for chain length determination of prenyltransferase reaction. J Biol Chem 271, 18831-7. (29) Guo, R. T., Kuo, C. J., Ko, T. P., Chou, C. C., Liang, P. H., and Wang, A. H. 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(1999) Geranyl diphosphate synthase: cloning, expression, and characterization of this prenyltransferase as a heterodimer. Proc Natl Acad Sci U S A 96, 13062-7. (34) Saiki, R., Nagata, A., Uchida, N., Kainou, T., Matsuda, H., and Kawamukai, M. (2003) Fission yeast decaprenyl diphosphate synthase consists of Dps1 and the newly characterized Dlp1 protein in a novel heterotetrameric structure. Eur J Biochem 270, 4113-21. (35) Saiki, R., Nagata, A., Kainou, T., Matsuda, H., and Kawamukai, M. (2005) Characterization of solanesyl and decaprenyl diphosphate synthases in mice and humans. FEBS J 272, 5606-22. (36) Sagami, H., Morita, Y., and Ogura, K. (1994) Purification and properties of geranylgeranyl-diphosphate synthase from bovine brain. J Biol Chem 269, 20561-6. (37) Kathryn L. Kavanagh, J. E. D., Gabor Bunkoczi, R. Graham G. Russell and Udo Oppermann. 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(42) Eftink, M. R. (1995) Use of multiple spectroscopic methods to monitor equilibrium unfolding of proteins. Methods Enzymol. 259, 487-512. (43) Chien, C. H., Huang, L. H., Chou, C. Y., Chen, Y. S., Han, Y. S., Chang, G. G., Liang, P. H., and Chen, X. (2004) One site mutation disrupts dimer formation in human DPP-IV proteins. J. Biol. Chem. 279, 52338-52345. (44) Kuo, C. J., Chi, Y. H., Hsu, T. A., and Liang, P. H. (2004) Characterization of SARS mian protease and inhibitor assay using a fluorogenic substrate. Biochem. Biophy. Res. Commun. 318, 862-867. (45) Hsu, M. F., Kuo, C. J., Chang, K. T., Chang, H. C., Chou, C. C., Ko, T. P., Shr, H. L., Chang, G. G., Wang, A. H.-J., and Linag, P. H. (2005) Mechanism of the maturation process of SARS-CoV 3CL protease. J. Biol. Chem. 280, 31257-31266. (46) Liang, P. H., Brun, K. A., Filed, J. A., O’nnell, K., Doyl, M. L., Green, S. M., Baker, A. E., Blcakburn, M. N., and Abdell-Meguid S. S. (1998) Site-directed mutagenesis probing the catalytic role of Arginines 165 and 166 of human cytomegalovirus protease. Biochemistry 37, 5923-5929. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/28775 | - |
| dc.description.abstract | 四異戊二烯焦磷酸合成酶 (geranylgeranyl pyrophosphate synthase) 可催化一個異戊二烯焦磷酸與法呢基焦磷酸 (farnesyl pyrophosphate) 反應產生四異戊二烯焦磷酸 (geranylgeranyl pyrophosphate)，此產物是四異戊二烯化 (geranylgeranylated)蛋白質、胡蘿蔔素 (carotenoid)、細胞膜脂質等－這些在生物體內重要分子的前趨物。從X光繞射光譜解出的立體結構來看，啤酒酵母的四異戊二烯焦磷酸合成酶是由15個α螺旋 (helix) 並以環狀物 (loop) 所連接構成其三級結構，並聚合成雙元體的四級結構。不同於其他已知的異戊二烯轉移酶 (trans-prenyl transferase) ，啤酒酵母的四異戊二烯焦磷酸合成酶具有一延伸至另一單元體 (subunit) 的N端胺基酸鍊。此胺基酸鍊包含第一個α螺旋和之後的環狀物，其構形與方向和其他一類異戊二烯轉移酵素相異並在雙體聚合中扮演關鍵性的角色。刪除前九個胺基酸導致酵素的雙體聚合瓦解，而刪除前十七個殘基更使酵素失去催化能力。我們更進一步證明刪除前七個殘基導致酵素瓦解成雙元體與單元體共存，刪除前八個殘基是完全破壞雙元體的聚合。為了找出哪個殘基是直接影響到酵素的雙體聚合，利用定點突變法來改變第七、第八和第九個殘基使其轉換成甘胺酸。透過分析型超高速離心機的實驗指出第七號麩胺酸突變為甘氨酸不改變其四級結構，第八號白胺酸突變為甘胺酸使酵素同時有單元體與雙元體的混合，第九號異白胺酸突變為甘胺酸導致雙元體完全瓦解成單元體。以雙定點突變法針對麩胺酸白胺酸與白胺酸異白胺酸改為甘胺酸亦形成單元體，證明第八號白胺酸與第九號異白胺酸對於酵素爽體聚合有不可或缺的貢獻。以單元體為主的突變蛋白比原始的蛋白少了近一千倍催化速率。第八和第九個殘基皆為疏水性胺基酸並形成疏水性聚集，因此對於其週遭環境的疏水性殘基進行分析。多點突變第一百六十三號白胺酸、第一百六十七號甲硫胺酸、第兩百號白胺酸、與第兩百零三號異白胺酸皆轉變為甘胺酸進行實驗，此一突變蛋白並不能摺疊正確導致形成所謂的包涵體。透過圓二色光譜儀的實驗發現單元體與雙元體的四異戊二烯焦磷酸合成酶具有極為相似的二級結構，但在熔點實驗顯示兩者間的熱穩定性並不一樣，雙元體酵素具有較高的熔點而突變單元體酵素熔點較低。此外對於雙定點突變法針對第二十二號白胺酸與第二十三號異白胺酸皆轉變為甘胺酸的酵素而言，此一突變導致雙元體部分瓦解成單元體說明位於第二α螺旋上的殘基不但接近雙元體聚合的界面且與聚合能力的強弱亦有關聯。位於第一N端α螺旋上的胺基酸距離雙元體聚合的界面有26 Å，卻對此酵素的四級結構與催化能力有如此顯著的影響，顯見蛋白四級結構的研究有很重要的意義。 | zh_TW |
| dc.description.abstract | Geranylgeranyl pyrophosphate synthase (GGPPs) catalyzes a condensation reaction of farnesyl pyrophosphate (FPP) with isopentenyl pyrophosphate (IPP) to generate C20 geranylgeranyl pyrophosphate (GGPP), which is a precursor for carotenoids, chlorophylls, geranylgeranylated proteins, and archaeal ether linked lipids. The 3-D structure of GGPPs from Saccharomyces cerevisiae is composed entirely of fifteen | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T00:22:09Z (GMT). No. of bitstreams: 1 ntu-96-R94b46035-1.pdf: 4825146 bytes, checksum: 74510747a3bca7b5a54774f0c16e1df8 (MD5) Previous issue date: 2007 | en |
| dc.description.tableofcontents | TABLE OF CONTENTS
中文摘要……………………………………………………………………………1 ABSTRACT…….……………………………………………………………………3 ABBREVIATION…………………………………………………………………….5 INTRODUCTION……………………………………………………………………6 MATERIAL AND METHODS……………………………………………………11 RESULTS……………………………………………………………………………18 DISCUSSION………………………………………………………………………22 REFERENCE………………………………………………………………………24 TABLE……………………………………………………………………………...32 FIGURE…………………………………………………………………………….35 | |
| dc.language.iso | en | |
| dc.subject | 雙體結構 | zh_TW |
| dc.subject | 酵母菌 四異戊二烯焦磷酸合成酶 | zh_TW |
| dc.subject | Dimerization S. cerevisiae Geranylgeranyl Pyrophosphate Synthase | en |
| dc.title | 長程交互作用調節酵母菌S. cerevisiae四異戊二烯焦磷酸合成酶之雙體結構 | zh_TW |
| dc.title | Long-Range Cooperative Interactions Modulate Dimerization in S. cerevisiae Geranylgeranyl Pyrophosphate Synthase | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 95-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳新,蔡明道 | |
| dc.subject.keyword | 酵母菌 四異戊二烯焦磷酸合成酶,雙體結構, | zh_TW |
| dc.subject.keyword | Dimerization S. cerevisiae Geranylgeranyl Pyrophosphate Synthase, | en |
| dc.relation.page | 62 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2007-07-27 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科學研究所 | zh_TW |
| 顯示於系所單位： | 生化科學研究所 | |
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