教師簡介

  • 專任教授
  • 周記源
  • Chi-Yuan Chou
  • 02-2826-7168 or 02-22826-7000 ext. 5789
  • cychou@ym.edu.tw
  • 傳統醫學大樓甲棟1F R108
  • 實驗室網頁
  • http://www.enzkin.org/
  • 專業領域
  • 蛋白質結構與功能、蛋白質二級、三級及四級結構分析、分子酵素學
  • 研究方向
  • (一)蛋白質的三級、四級結構。

    (二)蛋白質結構面臨物理性或化學性變 性時的變化過程,以及變性後是否能夠變回原來的構型。

    (三)蛋白質結構與功能之間的關聯性。

    (四)蛋白質之間或與其他生物分子如脂質或核酸間的作用。

    (五)酶的分子及催化模式探討。

  • 研究題目
  • (一)SARS與MERS冠狀病毒 (SARS and MERS coronavirus) 似木瓜素蛋白水解酶 (Papain-like protease) 的藥物發展 (Structure-based drug design)。

    (二)SARS與MERS冠狀病毒主蛋 白質水解酶 (Main protease) 的四級結構與催化活性的關係。

    (三)頭足動物晶體蛋白 (S-Crystallin) 與Glutathione S transferase的分子演化關係。

    (四)Biotin carboxylase 家族之蛋白質結構與功能探討。

  • 實驗室使用的主要技術
  • 我們主要是利用蛋白質表現載體(如pET-22,-24,-26,-28,-29)在大腸桿菌內表現大 量的蛋白質,之後利用層析法純化出所要表現的蛋白質,並用膠體電泳法分析蛋白質的純度,再利用紫外光光譜儀 (spectrophotometer) 或螢光光譜儀 (spectrofluorimeter) 測量酶的催化活性,之後利用軟體分析酶的酵素動力參數。在蛋白質二級、三級及四級結構分析上,分別利用圓偏振二旋光譜儀 (circular dichroism),螢光光譜儀,及分析型超高速離心機(analytical ultracentrifugation) 等進行測定、研究。針對一些特定的蛋白質與其作用分子的研究,會用結晶繞射 (X-ray crystallography) 的方法來解出該蛋白質與該作用分子的共同結構,以釐清其作用機轉。此外,實驗室尚有高效液相層析儀/多層次蛋白液相純化儀可用來分析小分子,或作蛋白質純化。在蛋白質分子 結構模擬方面,亦有電腦工作站可供分析。
  • 值得特別推薦的儀器設備及其使用目的
  • 分析型超高速離心機:主要是利用光譜儀即時在離心的過程中偵測物質的沉降,可以得知物質的四級結構組成 及其沉降常數、大致的質量;亦可用來量化分析生物分子 (Protein, DNA, lipid) 之間的相互作用。
  • 教授科目
  • 生命科學(一上):生命科學總論
    生命科學(二上):生物化學
    生化及細胞分子生物學(一)
    結構生物學(二)
    分子酵素學
    專題討論(碩)
  • 經歷
  • Feb, 2017-present
    國立陽明大學
    生命科學系暨基因體科學研究所
    教授
  • Aug, 2012-Jan, 2017
    國立陽明大學
    生命科學系暨基因體科學研究所
    副教授
  • Jul, 2008-Jul, 2012
    國立陽明大學
    生命科學系暨基因體科學研究所
    助理教授
  • Feb, 2007-Jun, 2008
    美國紐約哥倫比亞大學
    生物科學系
    博士後研究
  • Jun, 2005-Jan, 2007
    國立陽明大學
    生命科學系
    博士後研究
  • Aug, 1999-Jul, 2000
    國立臺灣大學附設醫院
    愛滋病防治中心
    研究助理
  • 學歷
  • 2005
    國防醫學院
    生命科學研究所 博士
  • 1999
    國立臺灣大學
    漁業科學研究所 碩士
  • 1995
    國立臺灣大學
    動物系漁業生物組 學士

代表著作

    Referred papers (*corresponding author)

    2018

  • Chuang, S. J., Cheng, S. C., Tang, H. C., Sun, C. Y., and Chou C. Y.* (2018) 6-Thioguanine is a noncompetitive inhibitor of human deubiquitinating protease USP2. Sci. Rep. 8: 3102. (2016 SCI impact factor: 4.259)
  • Lin, M. H., Moses, D. C., Hsieh, C. H., Cheng, S. C., Chen, Y. H., Sun, C. Y., and Chou C. Y.* (2018) Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes. Antiviral Res. 150, 155-163. (2016 SCI impact factor: 4.271)
  • Li, H. R., Chen, T. C., Hsiao, C. L., Shi, L., Chou C. Y., and Huang, J. R.* (2018) The physical forces mediating self-association and phase-separation in the C-terminal domain of TDP-43. BBA-Proteins Proteom. 1866, 214-223. (2016 SCI impact factor: 2.773)
  • 2017

  • Aik, E. S., Lin, M. H., Tan, D., Tripathy, A., Marzluff, W. F., Dominski, Z., Chou C. Y., and Tong. L.* (2017) The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3’-end processing. PLoS One 12(10): e0186034. (2016 SCI impact factor: 2.806)
  • 2016

  • Tan, W. H., Cheng, S. C., Liu, Y. T., Wu, C. G., Lin, M. H., Chen, C. C., Lin, C. H., and Chou C. Y.* (2016) Structure of a highly active cephalopod S-crystallin mutant: new molecular evidence for evolution from an active enzyme into lens-refractive protein. Sci. Rep. 6: 31176. (2015 SCI impact factor: 5.228)
  • Huang, C. W., Lin, H. C., Chou, C. Y., Kao, W. C., Chou, W. Y., and Lee, H. J.* (2016) Lys-315 at the interfaces of diagonal subunits of δ-crystallin plays a critical role in the reversibility of folding and subunit assembly. PLoS One 11(1): e0145957. (2015 SCI impact factor: 3.057)
  • Choi, P. H., Jo, J., Lin, Y. C., Lin, M. H., Chou, C. Y., Dietrich, L. E. P., and Tong, L.* (2016) A distinct holoenzyme organization for two-subunit pyruvate carboxylase. Nat. Commun. 7: 12713. (2015 SCI impact factor: 11.329)
  • Chen, Y. H., Chen, Y. J., Chou, C. Y., Wen, C. C., and Cheng, C. C.* (2016) UV-protective activities of pineapple leaves extract in zebrafish embryos. Res. Chem. Intermed. Accepted (2015 SCI impact factor: 1.833)
  • 2015

  • Ho, B. L., Cheng, S. C., Shi, L., Wang, T. Y., Ho, K. I., Chou, C. Y.* (2015) Critical assessment of the important residues involved in the dimerization and catalysis of MERS coronavirus main protease. PLoS One 10(12):e0144865. (2015 SCI impact factor: 3.057)
  • Cheng, K. W., Cheng, S. C., Chen, W. Y., Lin, M. H., Chuang, S. J., Cheng, I. H., Sun, C. Y.*, and Chou, C. Y.* (2015) Thiopurine analogues and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus. Antiviral Res. 115, 9-16. (2015 SCI impact factor: 4.909)
  • Tran, T. H., Hsiao, Y. S., Jo, J. Y., Chou, C. Y., Dietrich, L. E. P., Walz, T., and Tong, L.* (2015) Structure and function of a novel single-chain, multi- domain long-chain acyl-CoA carboxylase. Nature 518, 120-124. (2015 SCI impact factor: 38.138)
  • Chen, Y. H., Chou, C. Y., and Sun C. Y.* (2015) Impairment of the cellular distribution and stability of the erythropoietin receptor through the direct targeting of aristolochic acid. Toxicol. Sci. 147, 246-254. (2015 SCI impact factor: 3.880)
  • 2014

  • Chou, C. Y.*, Lai, H, Y., Chen, H. Y., Cheng, S. C., Cheng, K. W., and Chou, Y. W. (2014) Structural basis for catalysis and ubiquitin recognition by the severe acute respiratory syndrome coronavirus papain-like protease. Acta Crystallogr. D Biol. Crystallogr. 70, 572-581. (2015 SCI impact factor: 2.512)
  • Lin, M. H., Chuang, S. J., Chen, C. C., Cheng, S. C., Cheng, K. W., Lin, C. H., Sun, C. Y.*, and Chou, C. Y.* (2014) Structural and functional characterization of MERS coronavirus papain-like protease. J. Biomed. Sci. 21:54. (2015 SCI impact factor: 2.935)
  • Cheng, C. C.*, Chou, C. Y., Chang, Y. C., Wang, H. W., Wen, C. C., Chen, Y. H.* (2014) Protective role of comfrey leave extracts on UV-induced zebrafish fin damages. J. Toxicol. Pathol. 27, 115-121. (2015 SCI impact factor: 0.710)
  • 2013

  • Wu, C. G., Cheng, S. C., Chen, S. C., Li, J. Y., Fang, Y. H., Chen, Y. H., and Chou, C. Y.* (2013) Mechanism for controlling the monomer-dimer conversion of SARS coronavirus main protease. Acta Crystallogr. D Biol. Crystallogr. 69, 747-755. (2015 SCI impact factor: 2.512)
  • Yu, L. P. C., Chou, C. Y., Choi P. H., and Tong, L. (2013) Characterizing the importance of the biotin carboxylase domain dimer for Staphylococcus aureus pyruvate carboxylase catalysis. Biochemistry 52, 488-496. (2015 SCI impact factor: 2.876)
  • 2012

  • Chou, Y. W., Cheng, S. C., Lai, H. Y., and Chou, C. Y.* (2012) Differential domain stability of the severe acute respiratory syndrome coronavirus papain-like protease. Arch. Biochem. Biophys. 520, 74-80. (2015 SCI impact factor: 2.807)
  • Fan, C., Chou, C. Y., Tong, L., and Xiang, S.* (2012) Crystal structure of urea carboxylase provides insights into the carboxyltransfer reaction. J. Biol. Chem. 287, 9389-9398. (2015 SCI impact factor: 4.258)
  • 2011

  • Lai, Y. Y., Pai, C. W., Tsai, I. T., Chou, C. Y., Tsai, C. T., and Chen Y. H.* (2011) Molecular structure and developmental expression of zebrafish atp2a genes. Genes Genom. 33, 541-548. (2015 SCI impact factor: 0.692)
  • Tang, H. K., Chen, K. C., Liou, G. G., Cheng, S. C., Chien, C. H., Tang, H. Y., Huang, L. H., Chang, H. P., Chou, C. Y.*, and Chen, X.* (2011) Role of a propeller loop in the quaternary structure and enzymatic activity of prolyl dipeptidases DPP-IV and DPP9. FEBS Lett. 585, 3409-3414. (2015 SCI impact factor: 3.519)
  • Chou, C. Y., and Tong, L.* (2011) Structural and biochemical studies on the regulation of biotin carboxylase by substrate inhibition and dimerization. J. Biol. Chem. 286, 24417-24425. (2015 SCI impact factor: 4.258)
  • Chou, C. Y.*, Hsieh, Y. H., and Chang, G. G. (2011) Applications of analytical ultracentrifugation to protein size-and-shape distribution and structure-and-function analyses. Methods 54, 76-82. (2015 SCI impact factor: 3.503)
  • Hsieh, Y. H. and Chou, C. Y.* (2011) Structural and functional characterization of human apolipoprotein E 72-166 peptides in both aqueous and lipid environments. J. Biomed. Sci. 18:4. (2015 SCI impact factor: 2.935)
  • Chou, C. Y.*, Hsu, C. H., Wang, Y. H., Chang, M. Y., Chen, L. C., Cheng, S. C., and Chen, Y. H.* (2011) Biochemical and structural properties of zebrafish Capsulin produced by Escherichia coli. Protein Express. Purif. 75, 21-27. (2015 SCI impact factor: 1.407)
  • Chen Y. H.*, Wen C. C., Lin C. Y., Chou C. Y., Yang Z. S., and Wang Y. H. (2011) UV-induced fin damage in zebrafish as a system for evaluating the chemopreventive potential of broccoli and cauliflower extracts. Toxicol. Mech. Methods 21, 63-69. (2015 SCI impact factor: 1.476)
  • Yang, C. N., Shiao, Y. J., Shie, F. S., Guo, B. S., Chen, P. H., Chou, C. Y., Chen, Y. J., Huang, F. L., and Tsay, H. J. (2011) Mechanism mediating oligomeric A clearance by naive primary microglia. Neurobiol. Dis. 42, 221-230. (2015 SCI impact factor: 4.856)
  • 2010

  • Cheng, S. C., Chang, G. G., and Chou, C. Y.* (2010) Mutation of Glu-166 blocks the substrate-induced dimerization of SARS coronavirus main protease. Biophys. J. 98, 1327-1336. (2015 SCI impact factor: 3.632)
  • 2009

  • Chou, C. Y., Yu, L.P., and Tong, L.* (2009) Crystal structure of biotin carboxylase in complex with substrates and implications for its catalytic mechanism. J. Biol. Chem. 284, 11690-11697. (2015 SCI impact factor: 4.258)
  • 2008

  • Chou, C. Y., Chien, C. H., Han, Y. S., Prbanda, M. T., Hsieh, H. P., Turk, B., Chang, G. G., and Chen X.* (2008) Thiopurine analogs inhibit papain-like protease of severe acute respiratory syndrome coronavirus. Biochem. Pharmacol. 75, 1601-1609. (2015 SCI impact factor: 5.091)
  • Lin, P. I., Chou, C. Y., Chang, H. C., Hsu, W. C., Chang, G. G.* (2008) Correlation between dissociation and catalysis of SARS-CoV main protease. Arch. Biochem. Biophys. 472, 34-42. (2015 SCI impact factor: 2.807)
  • 2007

  • Bai, Y., Auperin, T. C., Chou, C. Y., Chang, G. G., Manley, J. L., and Tong, L.* (2007) Crystal structure of murine CstF-77: Dimeric association and implications for polyadenylation of mRNA precursors. Mol. Cell 25, 863-875. (2015 SCI impact factor: 13.958)
  • Chang, H. P., Chou, C. Y., and Chang G. G.* (2007) Reversible unfolding of the severe acute respiratory syndrome coronavirus main protease in guanidinium chloride. Biophys. J. 92, 1374-1383. (2015 SCI impact factor: 3.632)
  • Su, K. L., Wen, T. H., Chou, C. Y., Chang, G. G., Liu, G. Y., Hung, H. C.* (2007) Structural variation manipulates the differential oxidative susceptibility and conformational stability of apolipoprotein E isoforms. Proteins 68, 363-374. (2015 SCI impact factor: 2.499)
  • Lee, H. J., Chen, Y. S., Chou, C. Y., Chien, C. H., Lin, C. H., Chang, G. G., and Chen, X.* (2007) Investigation of the dimer interface and substrate specificity of prolyl dipeptidase DPP8. J. Biol. Chem. 281, 38653-38662. (2015 SCI impact factor: 4.258)
  • 2006

  • Chou, C. Y., Jen, W. P., Hsieh, Y. H., Shiao, M. S., and Chang, G. G.* (2006) Structural and functional variations in human apolipoprotein E3 and E4. J. Biol. Chem. 281, 13333-13344. (2015 SCI impact factor: 4.258)
  • Shen, Y., Chou, C. Y., Chang, G. G., and Tong, L.* (2006) Is dimerization required for the catalytic activity of bacterial biotin carboxylase? Mol. Cell 22, 807-818. (2015 SCI impact factor: 13.958)
  • Chien, C. H., Chai, C. H., Lin, C. H., Chou, C. Y., and Chen, X.* (2006) Identification of hydrophobic residues critical for DPP-IV dimerization. Biochemistry 45, 7006-7012. (2015 SCI impact factor: 2.876)
  • 2005

  • Chou, C. Y., Lin, Y. L., Huang, Y. C., Sheu, S. Y., Lin, T. H., Tsay, H. J., Chang, G. G.*, and Shiao, M. S.* (2005) Structural variation in human apolipoprotein E3 and E4: secondary structure, tertiary structure, and size distribution. Biophys. J. 88, 455-466. (2015 SCI impact factor: 3.632)
  • Hsu, W. C., Chang, H. C., Chou, C. Y., Tsai, F. J., Lin, P. I., and Chang, G. G.* (2005) Critical assessment of important regions in the subunit association and catalytic action of the severe acute respiratory syndrome coronavirus main protease. J. Biol. Chem. 280, 22741-22748. (2015 SCI impact factor: 4.258)
  • 2004

  • Chou, C. Y., Chang, H. C., Hsu, W. C., Lin, T. Z., Lin, C. H., and Chang, G. G.* (2004) Quaternary structure of the severe acute respiratory syndrome (SARS) coronavirus main protease. Biochemistry 43, 14958-14970. (2015 SCI impact factor: 2.876)
  • 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. (2015 SCI impact factor: 4.258)
  • 2001

  • Chou, C. Y., Horng, L. S., and Tsai, H. J.* (2001) Uniform GFP-expression in transgenic medaka (Oryzias latipes) at the F0 generation. Transgenic Res. 10, 303-315. (2015 SCI impact factor: 2.054)

    Revised, Submitted, and in preparation

  • Fang, Y. H., Cheng, S. C., and Chou, C. Y.* Half-of-the-sites reactivity in SARS coronavirus main protease. (In preparation)

    Review and Commentary (*co-equal author)

  • Chen, X.*, Chou, C. Y.*, and Chang, G. G. (2009) Thiopurine analogue inhibitors of severe acute respiratory syndrome – coronavirus papain-like protease, a deubiquitinating and deISGylating enzyme. Antivirial Chem. Chemother. 19, 151-156.
  • Chou, C. Y., Shiao, M. S., and Chang, G. G. (2004) Structural studies of the apolipoprotein E subdomains. The commentary for International Atherosclerosis Society (http://www.athero.org/commentaries/comm379.asp)