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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 梁博煌(Po-Huang Liang) | |
| dc.contributor.author | Ling-Yuan Chen | en |
| dc.contributor.author | 陳翎原 | zh_TW |
| dc.date.accessioned | 2021-06-13T04:41:56Z | - |
| dc.date.available | 2006-07-19 | |
| dc.date.copyright | 2006-07-19 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-18 | |
| dc.identifier.citation | [1] Liang, P.H., Ko, T.P., and Wang, A.H.-J. (2002) Structure, mechanism and function of prenyltransferases. Eur. J. Biochem. 269: 3339-3354.
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(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. [36] Chang, S. Y., Ko, T. P., Chen, A. P.-C., Chang, J. Y., Wang, A. H.-J. and Liang, P. H. (2004) Substrate Binding mode and reaction mechanism of undecaprenyl pyrophosphate synthase deduced from crystallographic studies. Protein Sci. 13, 971-978. [37] Chen, Y. H., Chen, A. P.-C., Chen, C. T., Wang, A. H.-J. and Liang, P. H. (2002) Probing the conformational change of Escherichia coli undecaprenyl pyrophosphate synthase during catalysis using an inhibitor and tryptophan mutants. J. Biol. Chem. 277, 7369-7376. [38] Marrero, P.F., Poulter, C.D., and Edwards, P.A. (1992) Effects of site-directed mutagenesis of the highly conserved aspartate residues in domain II of farnesyl diphosphate synthase activity. J. Biol. Chem. 267: 21873-21878. [39] Joly, A., and Edwards, P.A. 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Identification of the active conformation and the importance of length of the flexible loop 72-83 in regulating the conformational change of undecaprenyl pyrophosphate synthase. Biochemistry 42, 14452-14459. [57] Fersht, A. (1985) in Enzyme structure and mechanism. Chapter 5. The pH dependence of enzyme catalysis. pp 156. W. H. Freeman and Co., New York. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/33463 | - |
| dc.description.abstract | 類異戊二烯族化合物廣泛分布於自然界是由異戊二烯焦磷酸構成的聚合物。此類化合物的生合成是由一類異戊二烯轉移酵素所催化。這類酵素通常催化多個含5個碳異戊二烯焦磷酸和含15個碳的全反式法呢基焦磷酸結合生成長鏈產物。在一般細菌中,十一異戊二烯焦磷酸合成酵素產生的55個碳的產物可攜帶醣質以合成細菌胞壁peptidoglycan,因此酵素的活性抑制劑可作為抗生素藥物。然而在肺結核桿菌中,存在一新奇短順式法呢焦磷酸合成酶,可催化含10 個碳geranyl焦磷酸和異戊二烯焦磷酸結合生成含一順式雙鍵的法呢焦磷酸並以此為原料使用十異戊二烯焦磷酸合成酶來合成含50個碳的十異戊二烯焦磷酸。 本篇論文研究此二酵素反應機制及動力學,進而使用電腦模擬尋求發展抑制其活性的小分子。 | zh_TW |
| dc.description.abstract | Isoprenoids are widely distributed natural polymers containing isopentenyl pyrophosphate (IPP) as building block. The biosyntheses of isoprenoids are carried out by a group of enzymes called prenyltransferases which catalyze the head to tail condensation between IPP and farnesyl pyrophosphate (FPP) to make linear long-chain products. In bacteria, by using all-trans FPP, the C55 undecaprenyl pyrophosphate (UPP) generated by UPP synthase (UPPs) serves as a lipid carrier to transport lipid II across the bacterial cell membrane for peptidoglycan synthesis of the cell wall. However, in M. tuberculosis, a novel short-chain FPP synthase (FPPs) was found to catalyze the condensation between 10-carbon geranyl pyrophosphate and IPP to form a cis double bond. From this ω,E,Z-FPP, a C50 long-chain decaprenyl pyrophosphate (DPP) is synthesized by the decaprenyl pyrophosphate synthase (DPPs) as the lipid carrier in M. tuberculosis. In this thesis, I describe the mechanistic and kinetic caracterization of this novel FPPs as well as the DPPs. For developing anti- M. tuberculosis drug, we used the crystal structure of UPPs as a template and performed computer screening to search for the small molecule inhibitors of the M. tuberculosis FPPs and DPPs. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T04:41:56Z (GMT). No. of bitstreams: 1 ntu-95-R93b46025-1.pdf: 1031298 bytes, checksum: 9252cf387cb653897fdacd06344b7154 (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | ABSTRACT………………………………………………………………………….. 4
ABBREVIATIONS……………………………………………………………………6 INTRODUCTION ………...…………………………………………………………. 7 MATERIALS AND METHODS ………...…………………………………………..12 RESULTS ………...………………………………………………………………….26 DISCUSSION ………..……………………………………………………………...36 TABLES ………..……………………………………………………………………40 FIGURES …………………………………………………………………………....43 REFERENCES ………...…………………………………………………………….65 | |
| dc.language.iso | en | |
| dc.subject | 結核桿菌 | zh_TW |
| dc.subject | 異戊二烯焦磷酸轉移酶 | zh_TW |
| dc.subject | DPPs | en |
| dc.subject | FPPs | en |
| dc.subject | cis-type prenyltransferases | en |
| dc.title | 結核桿菌短及長順式異戊二烯焦磷酸轉移酶的反應機制、動力學,及抑制劑研究 | zh_TW |
| dc.title | Mechanistic, kinetic and inhibitory studies of a short-chain and a long-chain cis-type prenyltransferases from M. tuberculosis. | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 孟子青(Tzu-Ching Meng),邱繼輝(Kay-Hooi Khoo) | |
| dc.subject.keyword | 結核桿菌,異戊二烯焦磷酸轉移酶, | zh_TW |
| dc.subject.keyword | cis-type prenyltransferases,FPPs,DPPs, | en |
| dc.relation.page | 74 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-19 | |
| 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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