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在這堂課中，需要閱讀原始研究文獻和回顧文獻，使用分子影像程式來觀看結構資料，以及思考評論現今於生化領域的研究主題。This class also requires reading primary research papers and review papers, viewing structural data with molecular graphics programs, and thinking critically about modern topics in biochemistry.
閱讀資料以課堂章節(L#)區分列於下表。許多閱讀資料選自於教科書： Voet, D., J. Voet. 《生物化學》，紐約：J. Wiley & Sons, 2004. ISBN: 0471250902。Readings by lecture session (L#) are listed in the table below. Many of the readings are from the required textbook: Voet, D., J. Voet. Biochemistry. New York: J. Wiley & Sons, 2004. ISBN: 0471250902.
| L1-L2 |
1：細胞的大小與組成，以及此與調節的關連性1: Size and Components of Cells and Implications with respect to Regulation |
必讀Required
Minton, Allen P. 〈在生理狀態中，巨分子群的影響與巨分子在生化反應中的限制〉。《生物化學期刊》 276, no. 14 (2001): 10577-10580.〉Minton, Allen P. "The Influence of Macromolecular Crowding and Macromolecular Confinement on Biochemical Reactions in Physiological Media."
Journal of Biological Chemistry 276, no. 14 (2001): 10577-10580.
Goodsell, D. S. 〈活細胞內部。〉 《生化科學趨勢》 16, no. 6 (June 1991): 203-6.Goodsell, D. S. "Inside a Living Cell." Trends Biochem Sci. 16, no. 6 (June 1991): 203-6. |
| L3-L14 |
2：脂肪酸合成酶 (FAS)，聚酮合成酶(PKS)，以及非核糖體多胜肽生成酶(NRPS)2: Fatty Acid Synthases (FAS), Polyketide Synthases (PKS), and Non-ribosomal Polypeptide Synthases (NRPS) |
必讀Required
Voet & Voet 教科書內脂肪酸合成酶章節 (pp. 682-690) ，或在你所擁有的教科書內相當於此章節的文章。Voet & Voet section on FAS (pp. 682-690) or the equivalent section in your biochemistry text.
Keating, T. A., and C. T. Walsh. 〈在聚酮和多胜肽抗生素生合成中，起始、延伸、以及終止策略〉 《化學生物學之當代輿論》 3 (1999): 598-606.Keating, T. A., and C. T. Walsh. "Initiation, Elongation, and Termination Strategies in Polyketide and Polypeptide Antibiotic Biosynthes." Current Opinion in Chemical Biology 3 (1999): 598-606.
Ranghan, V. S., A. K. Joshi, and S. Smith. 〈動物性脂肪酸合成酶之功能性拓樸學的對映〉 《生物化學》 40, no. 36 (2001): 10792-10799.Ranghan, V. S., A. K. Joshi, and S. Smith. "Mapping the Functional Topology of the Animal Fatty Acid Synthase." Biochemistry 40, no. 36 (2001): 10792-10799.
Voet & Voet. 教科書：《生物化學》 pp. 680-704.Voet & Voet. Biochemistry. pp. 680-704.
Brown, Michael S., and Joseph L. Goldstein. 〈膽固醇平衡中，受器所調節的路徑〉 《科學》 232 (1986): 34-47.Brown, Michael S., and Joseph L. Goldstein. "A Receptor-mediated Pathway for Cholesterol Homeostasis." Science 232 (1986): 34-47.
Brown, Michael S., and Joseph L. Goldstein. 〈受器調控膽固醇代謝〉 《科學》 191 (1976): 150-4.Brown, Michael S., and Joseph L. Goldstein. "Receptor-Mediated Control of Cholesterol Metabolism." Science 191 (1976): 150-4.
Mazur, Walsh, and Kelleher. 《生物化學》 42 (2003): 13393-13400. Mazur, Walsh, and Kelleher. Biochemistry 42 (2003): 13393-13400.
選讀Optional Readings
Tsuji, S. Y., N. Wu, and C. Khosla. 〈聚酮生合成中，模組間的溝通〉 《生物化學》 40, no. 8 (2001): 2317-2325.Tsuji, S. Y., N. Wu, and C. Khosla. "Intermodular Communication in Polyketide Synthases." Biochemistry 40, no. 8 (2001): 2317-2325.
Rozwarski, D. A., et al. 〈Isoniazid目標物 (InhA) 之NADH的修飾〉 《科學》 279 (1998): 98-102.Rozwarski, D. A., et al. "Modification of the NADH of the Isoniazid Target (InhA)." Science 279 (1998): 98-102.
Brown, M. S., and J. L. Goldstein. 〈受器調控之膽固醇代謝〉 《科學》 191 (1976): 150-154.Brown, M. S., and J. L. Goldstein. "Receptor-Mediated Control of Cholesterol Metabolism." Science 191 (1976): 150-154.
Song, W. S. et al. 〈核醣體新生的蛋白質，從信號辨識粒子轉移到轉位管道的調節中，Sec61alpha所扮演的腳色。〉 《細胞》 100 (2000): 333-343.Song, W. S. et al. "Role of Sec61alpha in the Regulated Transfer of the ribosome-nascent chain complex from the signal recognition particle to the translocation channel." Cell 100 (2000): 333-343.
Suo, Zucai, Huawei Chen, and Christopher T. Walsh. 〈乙烯輔酶A被Yersiniabactin合成酶之高分子量蛋白質1次單元水解：在四個乙烯酵素中間物的水解修飾過程中，藉由突變所得到的證據。〉《美國國家科學院學報》 97 (2000): 14188-14193. (Fidelity in PKS)Suo, Zucai, Huawei Chen, and Christopher T. Walsh. "Acyl-CoA Hydrolysis by the High Molecular Weight Protein 1 Subunit of Yersiniabactin Synthetase: Mutational Evidence for a Cascade of Four Acyl-Enzyme Intermediates during Hydrolytic Editing." PNAS 97 (2000): 14188-14193. (Fidelity in PKS) |
| L14-L25 |
3：轉譯：載入、起始、延長、以及終止 – 動作之機制；G蛋白質之導論：開關或啟動者3: Translation: Loading, Initiation, Elongation, and Termination - A Machine in Action; Introduction to G-proteins: Switches or Motors |
必讀Required
Voet & Voet 生化教科書內之章節轉譯，第 959-1004 頁。Voet and Voet. Biochemistry text chapter on Translation. pp. 959-1004.
Rodnina, M. V., T. Daviter, K. Gromadski, and W. Wintermeyer. 〈核醣體核醣核酸在核醣體中解碼時的結構動力學〉 《生物化學》 84, no. 8 (August 2002): 745-754. (Elongation Kinetics) (Review)Rodnina, M. V., T. Daviter, K. Gromadski, and W. Wintermeyer. "Structural Dynamics of Ribosomal RNA during Decoding on the Ribosome." Biochimie 84, no. 8 (August 2002): 745-754. (Elongation Kinetics) (Review)
Steitz, and Moore. 〈核糖核酸參與核醣體的功能〉 《自然》 418 (2002): 229-235. (回顧)Steitz, and Moore. "The Involvement of RNA in Ribosome Function." Nature 418 (2002): 229-235. (Review)
Noller. 《生物化學》 38 (1999): 945-951. (方法)Noller. Biochemistry 38 (1999): 945-951. (Methods)
Pape, Tillmann, Wolfgang Wintermeyer, and Marina V. Rodnina. 〈延長因子Tu依賴型之胺基酸乙烯結合到大腸桿菌核醣體之A位置的完整動力機制。〉 《歐洲分子生物學組織期刊》17 (1998): 7490-97. (方法)Pape, Tillmann, Wolfgang Wintermeyer, and Marina V. Rodnina. "Complete Kinetic Mechanism of Elongation Factor Tu-dependent Binding of Aminoacyl-tRNA to the A site of the E.coli Ribosome." EMBO J 17 (1998): 7490-97. (Methods)
Wang, L, Z Zhang, A Brock, PG Schultz. 〈在大腸桿菌之遺傳密碼上酮官能基的添加。〉 《美國國家科學院學報》 100, no. 1 (一月 7, 2003): 56-61. (方法)Wang, L, Z Zhang, A Brock, PG Schultz. "Addition of the Keto Functional Group to the Genetic Code of Escherichia coli." Proc Natl Acad Sci 100, no. 1 (January 7, 2003): 56-61. (Methods)
附加的參考文獻Additional References
Voet and Voet. 生化教科書內之章節〈轉譯〉 pp. 959-1004.Voet and Voet. Biochemistry text chapter on Translation. pp. 959-1004.
Newcomb, and Noller. 〈從在70S核醣體內的RNA位置，作16S核醣體RNA之直接氫氧基放射性探測〉 《生物化學》 38 (1999): 945-951.Newcomb, and Noller. "Direct Hydroxyl Radical Probing of the 16S Ribosome RNA in the 70S Ribosomes from Internal Positions of RNA." Biochemistry 38 (1999): 945-951.
Wilson, K. S., H. F. Noller. 〈轉譯引擎內之分子運動。〉 《細胞》92 (1998): 337-49.Wilson, K. S., H. F. Noller. "Molecular Movement Inside the Translational Engine." Cell 92 (1998): 337-49.
Ramakrishnan, V. 〈核醣體結構與轉譯機制〉 《細胞》108 (2002): 557-572.Ramakrishnan, V. "Ribosome Structure and the Mechanism of Translation." Cell 108 (2002): 557-572.
Vale, J. 〈G Proteins的一般性主題與分子運動。〉 《細胞生物期刊》 135 (1996): 291-302.Vale, J. "Common Themes of G Proteins and Molecular Motors." Journal of Cell Biology 135 (1996): 291-302.
Rodnina, et al. 〈核醣體上，轉譯之動力學。〉 《歐洲微生物學會聯合會微生物學評論》23 (1999) 317-333.Rodnina, et al. "Dynamics of Translation on the ribosome." FEMS Microbiol Reviews 23 (1999) 317-333.
tRNA 合成酶tRNA Synthetases
Silvian, et al. 〈從Ile-tRNA 合成酶結構與Mupirocin 洞悉轉譯修飾〉 《科學》 285 (1999): 77-79.Silvian, et al. "Insights into Editing from an Ile-tRNA Synthetase Structure with tRNAIle with Mupirocin." Science 285 (1999): 77-79.
Hendrickson, et al. 〈tRNA合成酶修飾中心之選擇性破壞所造成的錯誤〉 《生物化學》 39 (2000): 8180-8186.Hendrickson, et al. "Errors from Selective Disruption of the Editing Center of a tRNA Synthetase." Biochemistry 39 (2000): 8180-8186.
G-蛋白質G-Proteins
這些文獻提供了課堂上將會討論的GTP 依賴型延長與轉位的詳細機轉。助教將會於課堂上複習這些文獻。These papers provide the details of the mechanisms of GTP-dependent elongation and translocation that will be discussed in class. The TAs will go over these papers in recitation.
Pape, et al. 〈完整之延長因子Tu依賴型結合之動力機轉〉 《歐洲分子生物學組織期刊》 17 (1998): 7490-7497.Pape, et al. "Complete Kinetic Mechanism of Elongation Factor Tu-dependent binding." The EMBO Journal 17 (1998): 7490-7497.
Pape, et al. 〈在核醣體上，胺基酸tRNA於起始選擇與校對之誘發性切合〉 《歐洲分子生物學組織期刊》 18 (1999): 2800-3807.Pape, et al. "Induced fit in initial selection and proofreading of aa-tRNA on the ribosome." The EMBO Journal 18 (1999): 2800-3807.
Rodnina, et al. 〈延長因子G水解GTP驅動tRNA在核醣體上的運動〉 《自然》 385 (1997): 37-41.Rodnina, et al. "Hydrolysis of GTP by Elongation Factor G drives tRNA movement on the ribosome." Nature 385 (1997): 37-41.
胜肽鍵的形成Peptide Bond Formation
Niessen, et al. 〈在胜肽鍵合成中，核醣體活性之結構基礎〉 《科學》 289 (2000): 920-930.Niessen, et al. "The Structural Basis of Ribosome Activity in Peptide Bond Synthesis." Science 289 (2000): 920-930.
Muth, et al. 〈在核醣體轉移酶中心，腺嘌呤帶有中性pKa〉 《科學》 289 (2000): 947-949.Muth, et al. "A single Adenosine with a Neutral pKa in the Ribosome Transferase Center." Science 289 (2000): 947-949.
兩篇新的文獻對於上面兩篇文獻說明的機轉提出異議。Two new papers dispute the mechanism presented in the above two papers.
Thompson, et al. 〈分析50S核醣體次單位的胜肽轉移酶活化位上，在23S rRNA之A2451及G2447位置上的突變〉 《美國國家科學院學報》 98 (2001): 9002-7.Thompson, et al. "Analysis of Mutations at residues A2451 and G2447 of 23S rRNA in the Peptidyltransferase Active Site of the 50S Ribosomal Subunit." Proc. Natl. Acad. Sci. U.S.A. 98 (2001): 9002-7.
Xiong, L., N. Polacek, P. Sander, E. C. Bottger, and A. Mankin. 〈於核醣體胜肽轉移酶中心之Adenine2451的pKa 仍然難以捉摸〉 《RNA》 7, no. 10 (2001): 1365-1369.Xiong, L., N. Polacek, P. Sander, E. C. Bottger, and A. Mankin. "pKa of Adenine 2451 in the Ribosomal Peptidyl Transferase Center Remains Elusive." RNA 7, no. 10 (2001): 1365-1369. |
| L25-L35 |
4：地下密室：參與蛋白質折疊與分解之巨分子體系4: Crypts and Chambers: Macromolecular Machines involved in Protein Folding and Degradation |
必讀Required
Voet and Voet. 生化教科書內之章節8, pp. 191-205.Voet and Voet. Chapter 8, pp. 191-205.
Hartl, and Hartl. 〈分子Chaperones位於細胞質: 從新生鏈到折疊蛋白質〉 《科學》 295 (2002): 1852-1858. (回顧)Hartl, and Hartl. "Molecular Chaperones in the Cytosol: From Nascent Chain to Folded Protein." Science 295 (2002): 1852-1858. (Review)
Houry, W. A., D. Frishman, C. Eckerskorn, F. Lottspeich, and F. U. Hartl. 〈確認Chaperonin GroEL 於有機體內的受質〉 《自然》 402 (1999): 147-151. (方法文獻)Houry, W. A., D. Frishman, C. Eckerskorn, F. Lottspeich, and F. U. Hartl. "Identification of in vivo Substrates of the Chaperonin GroEL." Nature 402 (1999): 147-151. (Methods paper)
選讀Optional Readings
V., Daggett, and A. R. Fersht. 〈蛋白質摺疊有統一的機制嗎？〉 《生化科學趨勢》 28, no. 1 (Jan 2003): 18-25.V., Daggett, and A. R. Fersht. "Is there a Unifying Mechanism for Protein Folding?" Trends Biochem Sci 28, no. 1 (Jan 2003): 18-25.
Walter, S., and J. Buchner. 〈分子Chaperones – 細胞內的蛋白質摺疊機器〉 《應用化學國際版》 41 (2002): 1098-1113.Walter, S., and J. Buchner. "Molecular Chaperones - Cellular Machines for Protein Folding." Angew. Chem. Int. Ed. 41 (2002): 1098-1113.
Dougan, D. A., A. Mogk, and B. Bukau. 〈細菌內蛋白質折疊與分解：分解或不分解？這是一個問題〉 《細胞：分子生命科學》 59 (2002): 1607-1616.Dougan, D. A., A. Mogk, and B. Bukau. "Protein Folding and Degradation in Bacteria: To Degrade or Not to Degrade? That is the Question." Cell: Mol Life Sci 59 (2002): 1607-1616.
非必要，但有興趣可閱讀Not Required but Interesting Reading
蛋白質摺疊錯誤與疾病之概論：Overview of protein misfolding and disease:
Dobson. 〈棄除形狀:蛋白質摺疊與疾病〉 《自然》 418 (2002): 729-30.Dobson. "Getting out of Shape: Protein Folding and Disease." Nature 418 (2002): 729-30.
Stroud, Walter. 〈受質同時活化訊息辨識粒子以及受質接受器〉 《自然》 427 (2004): 215-220.Stroud, Walter. "Substrate Twinning Activates the Signal Recognition Particle and its Receptor." Nature 427 (2004): 215-220.
Frank. 〈訊息辨識粒子之結構與停止延長之核醣體交互作用〉 《自然》 427 (2004): 808-814.Frank. "Structure of the Signal Recognition Particle Interacting with the Elongation-arrested Ribosome." Nature 427 (2004): 808-814. |
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