移至主內容

微生物結構基因體研究

周三和 教授
美國西雅圖華盛頓大學博士
生命科學大樓1218室
04-22840468-235
shchou@nchu.edu.tw

2019(108.06.30)退休

國立中興大學 生物化學研究所 所長 2010/08~ 2016/07
國立中興大學 生物化學研究所 教授 1996/08~ 
國立中央大學 生命科學系 教授兼主任 2002/08~2004/07 
美國西雅圖華盛頓大學 生化高分子合成室 主任 1984/09~1994/08 
美國西雅圖華盛頓大學 生物化學研究所 副教授 1993/07~1996/08 
美國西雅圖華盛頓大學 生物化學研究所 助教授 1988/01~1993/06 
台北師範大學 化學系 助教 1975/09~1976/06

中興大學生化研究所周三和老師的實驗室即是以結構生物學為導向,並輔以生物体的功能研究。目前主要從事兩個微生物結構基因体學的研究,一為重要的植物病原菌Xanthomonas campestris (黑腐菌), 希望從中找出此一致病菌的病理成因及新型的蛋白質折壘; 另一為感染人類並為一超級抗藥性的致病菌Stenotrophomonus maltophilia, 希望利用最新抑制細菌群聚現象(Quorum sensing)的觀念, 找出可抑制病原菌產生致病性因子的藥物。由於目前大部份病原病都已對現有的抗生素都已產生抗藥性, 故利用此一新觀念找尋新型抗生素為一極重要的研究項目。而細菌訊息傳導機制亦為目前世界上極為熱門的一項研究題材。目前核甘酸的衍生物, 如c-AMP, c-GMP, c-di-GMP, c-di-AMP或ppGpp等都在細菌訊息傳導機制中扮演各種不同的角色. 而其中又以c-di-GMP此一衍生物在細菌的致病性程度扮演最重要的角色. c-di-GMP的產生被發現與細菌的群聚現象有很大的關聯, 而在Xanthomonas campestris中, 群聚現象被發現係由rpf基因群的蛋白組來負責細菌在群聚時的訊息傳導. 其中又以RpfF, RpfC, 及RpfG此三個蛋白扮演最重要的角色. RpfF蛋白被發現負責細菌群聚時所須的訊息分子的合成, RpfC被發現負責此訊息分子的接受, 而RpfG則負責c-di-GMP分子的濃度控制. 基本上, c-di-GMP的濃度大小由兩類蛋白來控制, 一類係含有GGDEF保留胺基酸的c-di-GMP合成酵素, 一類係含有EAL或HD-GYP保留胺基酸的c-di-GMP水解酵素. 而上述的RpfG則為一含有HD-GYP保留胺基酸的c-di-GMP水解酵素. 故Xanthomonas campestris的致病性與此一病菌的群聚效應終於可被聯繫在一起. 有趣的是, 一般病原菌中皆含有為數不少的此二類酵素, 如在Xanthomonas campestris或在Stenotrophomonus maltophilia皆含有二十個以上的此類酵素, 而RpfG蛋白最近亦被發現與其它含有GGDEF保留胺基酸的c-di-GMP合成酵素有很強的作用, 有些可促進其功能, 有些則可抑制其功能. 故此類蛋白之間的作用, 及其與c-di-GMP, c-di-AMP或ppGpp二級訊息傳遞分子之間的作用及功能整合是一個另人非常有興趣的課題. 本實驗室目前將以此類的課題為研究重心, 希望能將大部份所有與此類蛋白有關的複合体結構解析出來, 並以結構的觀點來瞭解細菌的訊息傳導機制. 希冀將來能研發出不致引起細菌抗藥性的新型抗生素. 
下圖為以上說明的一簡圖, 供大家參考. 此一圖形係由下一回顧性論文中取出並加以改進. 
He, Y.-W. & Zhang, L.-H. (2008). Quorum sensing and virulence regulation in Xanthomonas campestris. FEMS Microbiol. Rev. 32, 842-857. 

實驗室目前亦擬建立一個仿生抗体中心及仿生生物膜中心。由於利用X-ray晶体繞射雖然是一個極為有效的解析生化大分子結構的技術, 但如何得到有用的大分子晶体一直是結構生物學者的一大痛處. 有鑑於此, 目前世界上的趨勢是利用抗体與擬結晶的蛋白或核酸分子結合, 再將此複合体做結晶篩選. 由於抗体分子能將擬結晶的蛋白分子含有較動態的部份固定住, 故一般認為抗体分子將有效的促進不易結晶的蛋白或膜蛋白分子結晶. 但困難的是單株抗体取得很難, 一般都須將抗原注射到動物如牛、羊中, 並須等幾個月後再進行單株抗体的篩選. 所以往往都須花費很大並須等待半年以後才能得到所要的單株抗体. 故此一方式對於結構生物的研究並不容易. 但目前世界上已有一先進的仿生抗体技術, 可輕易的只須利用試管篩選出有效的單株抗体基因, 並可快速的在大腸桿菌中表達出此單株抗体. 在短短幾個星期中, 即可獲得大量的有效單株抗体, 而費用亦可大量減少. 估計此一技術將在此一領域造成革命性的改良. 本實驗室已掌握此一關鍵性技術, 相信配合此一技術, 上述的所有負責細菌訊息傳導機制中有關的蛋白結構將可被順利解出。

另外, 膜蛋白的功能及結構也一直是生命科學領域研究的瓶頸. 此乃因膜蛋白都俱有一段脂溶性的結構, 所以並不溶於水溶液中, 造成它們在水溶液中並無正確功能及無法得到其結構. 但諷刺的是, 膜蛋白卻又在生命科學領域中扮演了關鍵性的角色, 因為每一細胞都須藉著膜蛋白與外界進行物質交換, 以維持其生命狀態. 所以如何有效研究膜蛋白的功能與結晶是世界上所以生命科學研究人員的夢想. 目前有一仿生生物膜的奈米粒子技術可將膜蛋白有效的包裹在其中, 並發現此一系統可達到快速研究膜蛋白分子的功能. 本實驗室目前亦已掌握到此一關鍵性技術, 並擬應用此一技術在細菌訊息傳導中有關信號接受体膜蛋白的功能及結構研究。.

值得一提的是, 本實驗室在過去幾年得到充份的計畫支援(包括教育部第二梯次的大學追求卓越計畫、國科會、農委會、及衛生署等單位), 目前已建立一世界級的結構蛋白体研究中心, 包括各樣與結構生物學研究有關等的貴重儀器, 並配備各樣昂貴的電腦設備, 以快速解析生化分子的三度空間結構。進入本實驗室的同學將可學習到最先進的各式基因轉殖技術, 蛋白表達及純化, X-ray晶体結構決定或核磁共振結構解析等重要技術, 對同學將來的出路, 不管在學術界或產業界等, 都有很大的幫助。實驗室目前有專案助理教授一位,博士後研究二位, 博士班學生六位, 及碩士班學生五位, 同學們皆能互相幫忙, .相處融洽, 順利拿到學位 歡迎對此一跨領域有興趣的同學加入此一微生物結構基因体研究的大家庭。

 

上圖為花椰菜受到植物黑腐病原菌Xanthomonas campestris 產生的染感情形(右圖). 其整個基因体已被解析出(左圖), 吾人可從其中找尋出俱重要功能的基因, 並將其放大, 轉殖至大腸桿菌中大量表達, 以篩選其晶体. 再利用X-ray晶体繞射得到其繞射資料. 由此繞射資料, 吾人將可利用軟体計算出其可能的電子密度圖, 並由此得到此一基因產物可能的三度空間結構圖. 由於蛋白的功能與其結構習習相關, 吾人將可由其結構探討其能的功能並由實驗中再加以驗證!

 

上圖為本實驗室已解析出的一些蛋白的三度空間結構. 由於利用X-ray繞射解析生化大分子的三度空間結構在過去為一極艱難的工作, 但目前由於一些技術上的突破, 此一任務已變為相對容易許多. 本實驗室亦有碩士班學生在二年內即已解析出蛋白結構並發表論文者. 所以雖然同學們在過去可能沒有接觸到此一先進領域, 但是在本實驗室中將可接受到此一領域的訓練並進入此一生物科技中新藥研發最重要的一環!

 

上圖則為Clp蛋白的結構及其與c-di-GMP的結合情形. C-di-GMP為目前所發現在細菌中與其致病性有關最重要的傳遞分子. 其可控制細菌是否要產生致病性因子或以生物保護膜的形式存在. 而c-di-GMP到底如何執行此一重要功能目前尚無具体結論. 本實驗室目前已解析出一類屬於c-AMP接受体的類似蛋白 (Clp), 並發現其不與c-AMP結合, 卻為c-di-GMP的重要受体. 由於c-di-GMP已被發現與細菌的群聚效應及與病菌的致病因子的產生有很大的關聯, 故本實驗室在此一領域的發現相信對未來新型抗生素的研發將有很大的助益. 有興趣者請參閱本實驗室最近發表的論文: 
The c-AMP Receptor-Like Protein CLP is a Novel c-di-GMP Receptor Linking Cell-Cell Signaling to Virulence Gene Expression in Xanthomonas campestris. Journal of Molecular Biology, 396, 646-662, 2010.

A.期刊論文

  1. Shan-Ho Chou* & Michael Y. Galperin*, “(Review) Diversity of c-di-GMP-binding proteins and mechanisms,” J. Bacteriology, vol.198(1), no.32-46, 2016.

 

  2. Hang Zhou, Cao Zheng, Jianmei Su, Bo Chen, Yang Fu, Yuqun Xie, Qing Tang, Shan-Ho Chou, Jin He, “Characterization of a natural triple tandem c-di-GMP riboswitch and application of the riboswitch-based dual-fluorescence reporter,” Scientific Reports, vol.6, 2016.

 

  3. Lynn Naughton, Shi-qi An, Ingyu Hwang, Shan-Ho Chou, Yong-Qian He, Ji-Liang Tang, Robert P. Ryan and J. Maxwell Dow, “(Review) Functional and genomic insights into the pathogenesis of Burkholderia species to rice,” Environmental Microbiology, vol.18, no.780-790, 2016.

 

  4. Jianmei Su, Xia Zou, Liangbo Huang, Tenglong Bai, Meng Yuan, Shan-Ho Chou, Ya-Wen He, Haihong Wang, Jin He, “DgcA, a diguanylate cyclase from Xanthomonas oryzae pv. oryzae regulates bacterial pathogenicity on rice.,” Scientific Reports, vol.6, 25978; doi: 10.1038/srep259, 2016. (SCI)

 

  5. Ruping Wang, Huiyong Xu, Feifei Xu, Liangcheng Du, Yuemao Shen, Shan-Ho Chou, Hongxia Liu, Youzhou Liu, Fengquan Liu* and Guoliang Qian*, “ TonB-dependent receptor 7 is a key factor regulated by LuxR solo and controls the antifungal HSAF biosynthesis in Lysobacter enzymogenes OH11,” Scientific Reports, vol.6, 26881, doi: 10.1038/srep268, 2016. (SCI)

 

  6. Huiyong Xu, Hongfu Chen, Yuemao Shen, Liangcheng Du, Shan-Ho Chou, Hongxia Liu , Guoliang Qian* and Fengquan Liu*, “Direct regulation of extracellular chitinase production by the transcription factor LeClp in Lysobacter enzymogenes OH11,” Phytopathology, 2016. (SCI)

 

  7. Yu-Chuan Wang, Ko-Hsin Chin, Zhi-Le Tu, Jin He, Christopher J. Jones, David Zamorano Sanchez, Fitnat H. Yildiz, Michael Galperin, & Shan-Ho Chou*, “Nucleotide binding by the widespread high-affinity cyclic di-GMP receptor MshEN domain.,” Nature Communications, 2016. (SCI)

 

  8. Yuan-Chao Lou, Yi-Fen Kao, Ko-Hsin Chin, Jen-Kang Chen, Je-Le Tu, Chinpan Chen* & Shan-Ho Chou* , “Backbone resonance assignments of the 54 kDa dimeric C-terminal domain of murine STING in complex with DMXAA,” Biomolecular NMR Assignments, vol.9, pp.271–274, 2015.

 

  9. Ko-Hsin Chin, Juin-Ming Liang, Jauo-Guey Yang, Min-Shao Shih, Zhi-Le Tu, Yu-Chuang Wang, Xing-Han Sun, Nien-Jen Hu, Zhao-Xun Liang, J Maxwell Dow, Robert P Ryan, Shan-Ho Chou*, “Structural insights into the distinct binding mode of cyclic di-AMP with SaCpaA-RCK,” Biochemistry, vol.54, pp.4936−4951, 2015.

 

  10. Yi-Chung Liu, Shiuh-Chaun Wang, Yu-Jen Yu, Kit-Man Fung, Ming-Te Yang, Yi-Hsiung Tseng, Shih-Feng Tsai, H Sunny Sun*, Ping-Chiang Lyu*, Shan-Ho Chou*, “Complete Genome Sequence of Xanthomonas campestris pv. campestris Strains 17 from Taiwan,” Genome Announcements, vol.6, 2015.

 

  11. Yuan-Chao Lou, Tsai-Hsuan Weng, Yi-Chuan Li, Yi-Fen Kao, Shan-Ho Chou, Chwan-Deng Hsiao and Chinpan Chen*, “Structure and dynamics of the polymyxin-resistance-associated response regulator PmrA in complex with the promoter DNA,” Nature Communications, vol.6, no.8838, 2015. (SCI)

 

  12. Yuan-Chao Lou, Iren Wang, M. Rajasekaran, Yi-Fen Kao, Meng-Ru Ho, Shang-Te Danny Hsu, Shan-Ho Chou, Shih-Hsiung Wu and Chinpan Chen*, “Solution Structure and Tandem DNA Recognition of the C-terminal Effector Domain of PmrA from Klebsiella pneumoniae.,” Nucleic Acids Research, vol.42, 4080-4093, 2014. (SCI)

 

  13. Sheng-Chia Chen, Chi-Hung Huang, Chia Shin Yang, Shu-Min Kuan, Ching-Ting Lin, Shan-Ho Chou & Yeh Chen*, “Crystal Structure of a Conserved Hypothetical Protein MJ0927 from Methanocaldococcus jannaschii Reveals a Novel Quaternary Assembly in the Nif3 family,” BioMed Research International, 2014. (SCI)

 

  14. Ko-Hsin Chin, Zhi-Le Tu, Yi-Che Su, Yu-Jen Yu, Hui-Chen Chen, Yuan-Chao Lo, Chin-Pan Chen, Glen Barber, Mary Lay-Cheng Chuah, Zhao-Xun Liang & Shan-Ho Chou*, “Novel c-di-GMP recognition modes of the mouse Innate Immune adaptor protein STING,” Acta. Crystallogr., vol.D69, 352-366., 2013. (SCI)

 

  15. Shi-Qi An, Ko-Hsin Chin, Melanie Febrer, Yvonne McCarthy, Jauo-Guey Yang, Chung-Liang Liu, David Swarbreck, Jane Rogers, J. Maxwell Dow, Shan-Ho Chou*, & Robert P. Ryan*, “A cyclic GMP-dependent signaling pathway regulates bacterial phytopathogenesis via a cyclic GMP-responsive diguanylate cyclase,” EMBO J., 2013. (SCI)

 

  16. Shi-Qi An, Ko-Hsin Chin, Melanie Febrer, Yvonne McCarthy, Jauo-Guey Yang, Chung-Liang Liu, David Swarbreck, Jane Rogers, J. Maxwell Dow, Shan-Ho Chou*, & Robert P. Ryan*, “A cyclic GMP-dependent signaling pathway regulates bacterial phytopathogenesis via a cyclic GMP-responsive diguanylate cyclase.,” EMBO J., vol.32, 2430-2438., 2013. (SCI)

 

  17. Yi-Tien Liao, Ko-Hsin Chin, Mary Lay-Cheng Chuah, Zhao-Xun Liang & Shan-Ho Chou*, “On the crystallization and preliminary X-ray diffraction characterization of FimXEAL-c-di-GMP and FimXEAL-c-di-GMP-PilZ complexes from Xanthomonas campestris .,” Acta Crystallogr., vol.F68, 301-305., 2012. (SCI)

 

  18. Yi-Che Su, Zhi-Le Tu, Chao-Yu Yang, Ko-Hsin Chin, Mary Lay-Cheng Chuah, Zhao-Xun Liang & Shan-Ho Chou*, “Crystallization Studies of the Murine c-di-GMP Sensor Protein STING.,” Acta Crystallogr., vol.F68, 906-910., 2012. (SCI)

 

  19. Ko-Hsin Chin, Wei-Ting Kuo, Yu-Jen Yu, Yi-Tien Liao, Ming-Te Yang, Mary Lay-Cheng Chuah, Zhao-Xun Liang & Shan-Ho Chou*, “Structural Polymorphism of c-di-GMP Bound to an EAL Domain and in Complex with a Type II PilZ domain Protein.,” Acta. Crystallogr., vol.D68, 1380-1392., 2012. (SCI)

 

  20. Qi Yaning, Linghui Xu, Xueming Dong, Yin Hoe Yau, Chun Loong Ho, Siew Lee Koh, Susana Geifman Shochat, Shan-Ho Chou, Kai Tang, Zhao-Xun Liang, “Functional Divergence of FimX in PilZ binding and Type IV Pili Regulation.,” J. Bacteriology., vol.194, 5922-5931., 2012. (SCI)

 

  21. Chao-Yu Yang , Ko-Hsin Chin , Zhao-Xun Liang , Andrew H.-J. Wang & Shan-Ho Chou*, “The Structure and Inhibition of a GGDEF Diguanylate Cyclase Complexed with (c-di-GMP)2 at the Active Site,” Acta. Crystallogr, vol.D67, no.997-1008, 2011. (SCI)

 

  22. Shan-Ho Chou*, “Delicate conformational changes of a protein in the CRP family lead to dramatic functional changes via binding of an alternate secondary messenger molecule,” Virulence, vol.2, no.152-157, 2011. (SCI)

 

  23. Tso-Ning Li, Ko-Hsin Chin, Andrew H.-J. Wang & Shan-Ho Chou*, “A novel tetrameric PilZ domain structure from Xanthomonads,” PLoS ONE, vol.6, no.e22036, 2011. (SCI)

 

  24. Parameswaran Hariharan, Christopher Sudhahar, Shan-Ho Chou, Der-Hang Chin, “Lipid bilayer-mediated release of enediyne antibiotic from neocarzinostatin chromoprotein,” Biochemistry, vol.49, no.7722-7732, 2010. (SCI)

 

  25. Yi-Che Su, Ko-Hsin Chin, Gwan-Han Shen, Hui-Ling Shih, Andrew H.-J. Wang, & Shan-Ho Chou*, “Crystal Structure of Stenotrophomonas maltophilia FeoA Complexed with Zinc: A Procaryotic SH3 Domain-like Protein Possibly Serves as a Bacterial Ferrous Iron Transport Activating Factor,” Acta. Crystallogr, vol.F66, no.636-642, 2010. (SCI)

 

  26. Ko-Hsin Chin, Yen-Chung Lee, Zhi-Le Tu, Chih-Hua Chen, Yi-Hsiung Tseng, Jinn-Moon Yang, Robert P. Ryan, Yvonne McCarthy, J. Maxwell Dow, Andrew H.-J. Wang, & Shan-Ho Chou*., “The c-AMP Receptor-Like Protein CLP is a Novel c-di-GMP Receptor Linking Cell-Cell Signaling to Virulence Gene Expression in Xanthomonas campestris.,” J. Mol. Biol. , vol.396, 646-662. , 2010. (SCI)

 

  27. Parameswaran Hariharan, Christopher Sudhahar, Shan-Ho Chou, Der-Hang Chin*, “Lipid bilayer-mediated release of enediyne antibiotic from neocarzinostatin chromoprotein,” Biochemistry, vol.49, 7722-7732, 2010. (SCI)

 

  28. Jhe-Le Tu, Ko-Hsin Chin, Andrew H.-J. Wang, & Shan-Ho Chou*, “Unique GTP-binding Pocket and Allostery of UMP Kinase from a Gram-Negative Phytopathogen Bacterium,” J. Mol. Biol, vol.385, 1113–1126, 2009. (SCI)

 

  29. Tso-Ning Li, Ko-Hsin Chin, Jyung-Hurng Liu, Andrew H.-J. Wang & Shan-Ho Chou*, “XC1028 from Xanthomonas campestris Adopts a PilZ Domain-like Structure without a c-di-GMP Switch,” Proteins: Structure, Function, and Bioinformatics, vol.DOI: 10.1002/prot.22330, 2009. (SCI)

 

  30. Chao-Yu Yang, Ko-Hsin Chin, Ming-Te Yang, Andrew H.-J. Wang, & Shan-Ho Chou*, “Crystal Structure of RecX: A Potent Inhibitor Protein of RecA from Xanthomonas campestris,” Proteins: Structure, Function, and Bioinformatics, vol.74, 530-537, 2009. (SCI)

 

  31. Shu-Ju Liao,Chao-Yu Yang,Ko-Hsin Chin,Andrew H.-J. Wang and Shan-Ho Chou, “Insights into the Oxidoreduction Activity of Xanthomonas campestris Bacterioferritin Comigratory Protein from the Trapped Intermediate-Ligand Complex Structures,” J. Mol. Bio, vol.390, 951-966, 2009. (SCI)

 

  32. Tung-Yi Tsai ,Chao-Yu Yang ,Hui-Ling Shih ,Andrew H.-J. Wang ,and Shan-Ho Chou, “Xanthomonas campestris PqqD in the pyrroloquinoline quinone biosynthesis operon adopts a novel saddle-like fold that possibly serves as a PQQ carrier,” Proteins: Structure, Function, and Bioinformatics, vol.76, 1042-1048, 2009. (SCI)

 

  33. Xian-Ya Lin ,Shu-Ju Liao , Ko-Hsin Chin, Hui-Ling Shih ,Gwan-Han Shen , Andrew H.-J. Wang and Shan-Ho Chou, “Crystallization and preliminary X-ray diffraction characterization of RpfF ,a key DSF synthase from Stenotrophomonas maltophilia,” Acta Crystallogr Sect F: Struct Biol Cryst Commun , 2009. (SCI)

 

  34. Cheng-Nan Chen, Ko-Hsin Chin, Andrew H.-J. Wang, & Shan-Ho Chou*, “The First Crystal Structure of Gluconolactonase Important in the Glucose Secondary Metabolic Pathways,” J. Mol. Biol, vol.19;384(3):604-14, 2009. (SCI)

 

  35. Wei-Ting Kuo, Ko-Hsin Chin, Wen-Ting Lo, Andrew H.-J. Wang, & Shan-Ho Chou*, “Crystal Structure of the C-terminal Domain of a Flagellar Hook-Capping Protein from Xanthomonas campestris,” J. Mol. Biol, vol.381, 189-199, 2008. (SCI)

 

  36. Cheng-Jen Liao, Ko-Hsin Chin, Chao-Hsiung Lin, Peter Shi-Fong Tsai, Ping-Jiang Lyu, Chiu-Chong Young, Andrew H.-J. Wang, & Shan-Ho Chou*, “Crystal Structure of DFA0005 Complexed with a-Ketoglutarate: A Novel Member of theICL/PEPMSuperfamily from Alkali-tolerant Deinococcus ficus,” Proteins: Structure, Function, and Bioinformatics, vol.73, 362-371, 2008. (SCI)

 

  37. Ko-Hsin Chin, Sz-Kai Ruan, Andrew H.-J. Wang, & Shan-Ho Chou*, “XC5848, an ORFan protein from Xanthomonas campestris, adopts a novel variant of Sm-like motif,” Proteins: Structure, Function, and Bioinformatics, vol.68,1006-1010, 2007. (SCI)

 

  38. Ko-Hsin Chin, Ying-Der Tsai, Nei-Li Chan, Andrew H.-J. Wang, & Shan-Ho Chou*, “The crystal structure of XC1258 from Xanthomonas campestris: A CN-hydrolase superfamily protein with an arsenic adduct in the active site,” Proteins: Structure, Function, and Bioinformatics, vol.69,665-671, 2007. (SCI)

 

  39. Li-Ying Lin, Chung-Lun Ching, Ko-Hsin Chin, Shan-Ho Chou, and Nei-Li Chan, “Crystal structure of the conserved hypothetical cytosolic protein Xcc0516 from Xanthomonas campestris reveals a novel quaternary structure assembled by five four-helix bundles,” Proteins: Structure, Function, and Bioinformatics, vol.65, 783-786, 2006. (SCI)

 

  40. Ko-Hsin Chin, Chia-Cheng Chou, Cheng-Chung Lee, Andrew H.-J. Wang, & Shan-Ho Chou*, “Crystal structure of XC5357 from Xanthomonas campestris: A putative tetracenomycin polyketide synthesis protein adopting a novel cupin subfamily structure,” Proteins: Structure, Function, and Bioinformatics, vol.65, 1046-1050, 2006. (SCI)

 

  41. Ko-Hsin Chin, Chia-Cheng Chou, Cheng-Chung Lee, Andrew H.-J. Wang, & Shan-Ho Chou*, “The crystal structure of XC847 from Xanthomonas campestris: a 3’-5’ oligoribonuclease of DnaQ fold with a novel opposingly-shifted helix,” Proteins: Structure, Function, and Bioinformatics, vol.65, 1036-1040, 2006. (SCI)

 

  42. Ko-Hsin Chin, Zhi-Le Tu, Juo-Ning Li, Chia-Cheng Chou, Andrew H.-J. Wang, & Shan-Ho Chou*, “Crystal structure of an unliganded multiple antibiotic-resistance repressor (MarR) from Xanthomonas campestris,” Proteins: Structure, Function, and Bioinformatics, vol.65, 239-242, 2006. (SCI)

 

  43. Parameswaran Hariharan, Wenchuan Liang, Shan-Ho Chou, & Der-Hang Chin, “A new model for ligand release: Role of side-chain in gating the enediyne antibiotic,” J. Biol. Chem, vol.281, 16025-16033, 2006. (SCI)

 

  44. Ko-Hsin Chin, Chia-Cheng Chou, Andrew H.-J. Wang, & Shan-Ho Chou*, “The crystal structure of a putative acyl-CoA thioesterase from Xanthomonas campestris (XC229) adopts a tetrameric hotdog fold of mode,” Proteins: Structure, Function, and Bioinformatics, vol.64, 823-826, 2006. (SCI)

 

  45. Chiu-Yueh Chen, Yi-Chun Chen, Jenq-Chang Lee, Wenya Huang, Shan-Ho Chou, and Woei-Jer Chuang, “Preparation of amino-acid-type selective isotope labeling of protein expressed in Pichia pastoris,” Proteins: Structure, Function, and Bioinformatics, vol.62, 279-287, 2006. (SCI)

 

  46. Yan-You Wu, Ko-Hsin Chin, Chia-Cheng Chou, Cheng-Chung Lee, Hui-Lin Shr, Ping-Chiang Lyu, Andrew H.-J. Wang, & Shan-Ho Chou*, “The cloning, purification, crystallization, and preliminary X-ray crystallographic analysis of XC847, a 3'-5' oligoribonuclease from Xanthomonas campestris,” Acta. Crystallogr, vol.F61, 902-905, 2005. (SCI)

 

  47. Zhi-Le Tu, Juo-ning Li, Ko-Hsin Chin, Chia-Chen Chou, Cheng-Cheng Lee, Hui-Lin Shr, Ping-Chiang Lyu, Fei Philip Gao, Andrew H.-J. Wang, & Shan-Ho Chou*, “The cloning, expression, crystallization, and preliminary X-ray analysis of a putative multiple antibiotic-resistance repressor protein (MarR) from Xanthomonas campestris,” Acta. Crystallogr, vol.F61, 706-708, 2005. (SCI)

 

  48. Chao-Yu Yang, Ko-Hsin Chin, Chia-Chen Chou, Hui-Lin Shr, Fei Philip Gao, Ping-Chiang Lyu, Andrew H.-J. Wang, & Shan-Ho Chou*, “Cloning, purification, crystallization, and preliminary X-ray characterization of a conserved hypothetical protein XC6422 from Xanthomonas campestris,” Acta. Crystallogr, vol.F61, 703-705, 2005. (SCI)

 

  49. Chyao-Li Chu, Ko-Hsin Chin, Fu-Yang Lin, Chia-Chen Chou, Cheng-Cheng Lee, Hui-Lin Shr, Ping-Chiang Lyu, Andrew H.-J. Wang, & Shan-Ho Chou*, “A putative polyketide synthesis protein XC5357 from Xanthomonas campestris: heterologous expression, crystallization, and preliminary X-ray analysis ,” Acta. Crystallogr, vol.F61, 697-699, 2005. (SCI)

 

  50. Ko-Hsin Chin, Chia-Chen Chou, Cheng-Cheng Lee, Hui-Lin Shr, Ping-Chiang Lyu, Andrew H.-J. Wang, & Shan-Ho Chou*, “On the preparation, crystallization, and preliminary X-ray analysis of XC2382, an ApaG protein of unknown structure from Xanthomonas campestris,” Acta. Crystallogr, vol.F61, 700-702, 2005. (SCI)

 

  51. Ko-Hsin Chin, Zhao-Wei Huang, Kun-Chou Wei, Chia-Chen Chou, Cheng- Cheng Lee, Hui-Lin Shr, Fei Philip Gao, Ping-Chiang Lyu, Andrew H.-J. Wang, & Shan-Ho Chou*, “Preparation, crystallization, and preliminary X-ray characterization of a conserved hypothetical protein XC1692 from Xantho- monas campestris,” Acta. Crystallogr, vol.F61, 691-693, 2005. (SCI)

 

  52. Ko-Hsin Chin, Wei-Tien Kuo, Chia-Chen Chou, Hui-Lin Shr, Ping-Chiang Lyu, Andrew H.-J. Wang, & Shan-Ho Chou*, “Cloning, purification, crystalli- zation, and preliminary X-ray analysis of XC229, a conserved hypothetical protein from Xanthomonas campestris,” Acta. Crystallogr, vol.F61, 694-696, 2005. (SCI)

 

  53. Shan-Ho Chou*, Ko-Hsin Chin, & Andrew H.-J. Wang, “DNA Aptamers as Potential Anti-HIV Agents,” Trends in Biochemical Science, vol.30, 231-234, 2005. (SCI)

 

  54. Ko-Hsin Chin, Fu-Yang Lin, Yu-Chen Hu, Kong Hung Sze, Ping-Chiang Lyu & Shan-Ho Chou*, “Solution structure of a bacterial BolA-like protein XC975 from the plant pathogen Xanthomonas campestris pv. campestris,” J. Biomol. NMR, vol.31, 167-172, 2005. (SCI)

 

  55. Chen, F-M, F Sha, K-H Chin & S-H Chou* , “The nature of actinomycin D bind- ing to d(AACCAXYG) sequence motifs,” Nucleic Acids Res, vol.32, 271- 277, 2004. (SCI)

 

  56. Chen, F-M, F Sha, K-H Chin & S-H Chou*, “The nature of actinomycin D binding to self-complementary d(CXYGGCCY’X’G) sequence motifs,” Nucleic Acids Res, vol.31, 4238- 4246, 2003. (SCI)

 

  57. Chin, K-H, F-M Chen & S-H Chou*, “Solution structure of ActD/ 5’-CCG- TT3-GTGG-3’ complex: Drug interaction with tandem GT mismatches and hairpin loop backbone,” Nucleic Acids Res , vol.31, 2622-2629, 2003. (SCI)

 

  58. Chin, K-H & S-H Chou* , “Sheared ganti; Csyn base pair: A unique d(GXC) loop closure motif,” J Mol. Bio, vol.329, 351-361, 2003. (SCI)

 

  59. Chou*, S-H, K-H Chin & Andrew H-J Wang, “Unusual DNA hairpin and duplex motifs,” Nucleic Acids Res, vol.31, 2461-2474, 2003. (SCI)

 

  60. F-M Chen, F Sha, K-H Chin & S-H Chou* , “Binding of actinomycin D to single- stranded DNA of sequence motifs d(TGTCTnG) and d(TGTnGTCT),” Biophysical J, vol.8, 432-439, 2003. (SCI)

 

  61. Chou*, S-H, K-H Chin & F-M Chen, “Looped-out and perpendicular: deformation of Watson-Crick base pair associated with actinomycin D binding,” Proc Natl Acad Sci USA, vol.99, 6625-6630, 2002. (SCI)

 

  62. Chou*, S-H, K-H Chin & F-M Chen, “Looped-out and perpendicular: deformation of Watson-Crick base pair associated with actinomycin D binding,” Proc Natl Acad Sci USA, vol.99, 6625-6630, 2002. (SCI)

 

  63. Chou*, S-H & K-H Chin, “Quadruple-intercalated G-6 stack: A possible motif in the fold-back structure of Drosophila centromeric dodeca-satellite?,” J Mol Biol, vol.314, 139-152, 2001. (SCI)

 

  64. Chou*, S-H & K-H Chin, “Solution structure of a DNA double helix incorporateing a track of four consecutive non-Watson-Crick base pairs,” J Mol Biol , vol.312, 769- 781, 2001. (SCI)

 

  65. Chou*, S-H & K-H Chin, “Zipper-like Watson-Crick base pairs,” J Mol Biol , vol.312, 753-768, 2001. (SCI)

 

  66. Chou*, S-H & K-H Chin, “Novel cross-strand three-purine stack of the highly conserved 5’-GA/AAG-5’ internal loop in the 3’-end termini of parvovirus genomes,” J Biomol NMR , vol.21, 307-319, 2001. (SCI)

 

  67. Chou*, S-H, K-H Chin & C Chen, “Enhanced loop DNA folding induced by thy- mine-CH3 and perpendicular guanine-thymine interaction,” J Biomol NMR, vol.19, 33- 49, 2001. (SCI、EI)

 

  68. Tsao, Y-P, L-Y Wang, S-T Hsu, ML Jain, S-H Chou*, W-C Huang & J-W Cheng, “The solution structure of [d(CGC)r(amamam)d(TTTGCG)]2,” J Biomol NMR, vol.21, 209-220, 2001. (SCI)

 

  69. Chou*, S-H, Y-Y Tseng & B-Y Tsu, “Natural abundance heteronuclear NMR studies of the T3 mini-loop hairpin in the terminal repeat of adeno- associated virus 2,” J Biomol NMR, vol.17, 1-16, 2000. (SCI)

 

  70. Jayaraman G, TKS Kumar, C-C Tsai, S. Srisailam, S-H Chou, C-L Ho & C Yu, “Elucidation of the solution structure of cardiotoxin analogue V from the Taiwan cobra (Naja najaatra)-Identification of structural features important for the lethal action of snake venom cardiotoxins,” Protein Sci, vol.9, 637-646, 2000. (SCI)

 

  71. Tsu, S-T, M-T Chou, S-H Chou*, W-C Huang & JW Cheng, “ Hydration of [d(CGC)r(aaa)d(TTTGCG)]2,” J Mol Biol, vol.295, 1129-1137, 2000. (SCI)

 

  72. Tso-Ning Li, Ko-Hsin Chin, Andrew H.-J. Wang & Shan-Ho Chou, “A novel tetrameric PilZ domain structure from Xanthomonads,” PLoS ONE, vol.6, no. e22036. (SCI)

 

  73. Qing Tang, Hong-Liang Qian, You-Wen Zhao, Kang Yin, Xun Wang, Wen Wang, Shan-Ho Chou, Jin He, “Cyclic di-GMP contributes to adaption and virulence of Bacillus thuringiensis through a riboswitch-regulated collagen adhesion protein,” Scientific Reports, vol.6, 28807; doi: 10.1038/srep288. (SCI)

 

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