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鄭貽生 教授

E-mail:  chengys@ntu.edu.tw
電話: (02) 33662951 
專長: 蛋白質晶體結構、結構生物資訊 
學歷: 國防醫學院生命科學博士
研究室:  生命科學館1121室

近年研究主題 

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  1. 生質能源：綠竹纖維素合成酶之蛋白質結構與功能分析

  2. 表觀遺傳調控蛋白研究：植物去乙醯基酶HDAs之生化與生物物理研究

  3. 藥物設計與開發：MTH1之抑制劑結構及其抑制效率分析

研究室簡介

  • Fin219-FIP1 複合體結構與功能分析

FIN219(Far-red insensitive 219)又稱為JAR1(Jasmonate Resistant 1)，為一575個胺基酸組成的蛋白質，屬阿拉伯芥(Arabidopsis thaliana)GH3蛋白質家族。此蛋白於植物中透過將吲哚乙酸(indole-3-acetic acid, IAA)和茉莉酸(Jasmonic acid, JA)等植物賀爾蒙和胺基酸接合來調控賀爾蒙在植物體內的恆定性，進而影響到植物的生長發育以及抗病蟲害之能力。FIN219的功能可分為以下二個方向：
 

(i)  和光型態發生(Photomorphogenesis)有關
光形態發生由吸收紅光及遠紅光的光敏素和吸收UV-A及藍光的隱花色素所共同調控。在遠紅光照射下，阿拉伯芥的fin219突變體幼苗具有下胚軸伸長的外表型，並做為cop1的基因外抑制體(Hsieh et al., 2000)。另外，GST(glutathione S-transferases)蛋白質基因fip1(FIN219-interacting protein 1)，它所產生的蛋白質被證實可與FIN219的C端作用（Hsieh et al., 2007) 

 

(ii)  和植物賀爾蒙調節有關
茉莉酸在植物中扮演重要的訊息傳遞角色，其牽涉了生長發育、抗病蟲害以及植物傷的傳遞途徑。然而在分子層次上對於茉莉酸的了解十分有限，目前已知，植物中有許多茉莉酸和胺基酸接和的小分子，例如：JA-Leu，JA-Val和JA-Phe，係由JAR1催化茉莉酸和氨基酸接合，其中以JA和Ile的親和度最大。以JAR1的阿拉伯芥突變株jar1-1來說，添加JA-Ile在培養基中可抑制幼苗下胚軸的延長，這和JAR1的野生型具有一致性。JAZ(jasmonate ZIM-domain)蛋白質家族被認為是調控茉莉酸訊息傳遞的重要關鍵，JAZ1平時可以抑制茉莉酸反應相關基因(jasmonate-responsive gene)的轉錄，但經過茉莉酸處理後，會造成JAZ1在細胞核中的降解，進而促進茉莉酸反應相關基因的表現，其降解機制就是透過SCFCOI1 (Skp/Cullin/F-box complex)，一種泛素作用接合酶 (E3 ubiquitin ligase)，蛋白質間的交互作用完成。而促進Col1和JAZ1的交互作用產生的就是小分子JA-Ile，顯示JAR1可能是調控茉莉酸傳遞途徑以及相關蛋白質量上的重要樞紐。本研究成果發表於Proc. Natl. Acad. Sci. U.S.A. 114:E1815-E1824. Epub Feb 21, 2017

先前已完成的研究主題

蛋白質結構與功能是後基因體時代，極受重視的領域，由結構與功能分析提供分子層次的立體觀點。
我們運用蛋白質晶體學之技術，解析生物巨分子 (含DNA、RNA及蛋白質)之三維結構，探討結構、功能、分子演化及相關生物訊息。
目前我們的研究方向為：

1.生質能源：
綠竹纖維素合成酶之蛋白質結構與功能分析植物細胞壁主要由纖維素(cellulose)、半纖維素(hemicellulose)、果膠(pectin)、及二次代謝物所組成。纖維素佔細胞壁組成50%以上，是地球上含量最豐富的生物質(biomass)。植物細胞負責生產纖維素的酵素為纖維素合成酶複合體(cellulose synthase complex, CSC)，其中纖維素合成酶(cellulose synthase, CesA)是催化核心，作為合成長鏈糖供纖維素合成酶複合體產出微纖維(microfibril)，並進一步形成植物細胞壁。竹子是生長速度最快的植物，日平均生長可達25公分，顯示其纖維素合成也需要配合其生長速度。本研究分析綠竹纖維素合成酶(Bambusa oldhamii Cellulose synthases, BoCesAs)之蛋白質結構與其生物物理特性，綠竹纖維素合成酶有10種(BoCesA1~10)，目前已利用酵母菌表現系統，醱酵槽大量培養及蛋白質快速純化儀成功表現BoCesA1, 2, 3, 4, 5 及 7等蛋白，將陸續進行後續酵素活性分析方法之開發，蛋白質結晶結構分析及相關生物物理的研究。終極目標是解析綠竹纖維素合成酶複合體的結構，以探究植物纖維素合成的分子機制。 

2.表觀遺傳調控蛋白研究：
植物去乙醯基酶HDAs之生化與生物物理研究組蛋白去乙醯基酶(Histone deacetylases, HDAs)參與調控植物生長、發育與植物回應逆境反應所需的基因表現。HDAs的酵素活性作用為移除組蛋白上之乙醯基，促使組蛋白與DNA形成緊密結合，結果將造成染色質濃縮使位於該區域的基因無法表現。在阿拉伯芥共有18個HDA，可分為三個家族：分別為RPD3/HDA1-like家族，HD2家族及Sirtuin家族，其中RPD3/HDA1-like家族成員最多，可以細分為三群，本研究主要針對第二群的HDA5, HDA15及HDA18進行研究。其他HDAs亦將陸續進行研究。目前我們已將第二群的去乙醯基酶活性區域分別構築出來，並進行活性分析比較與蛋白質結構解析，其中HDA15的活性與聚合形式受其N端及C端的影響，有助於了解其分子作用機制方式。由於表觀遺傳研究近幾年來研究十分熱門，其交互作用的蛋白質相當多，因此本研究主題除探討HDAs結構外，亦將會針對相關HDAs的結合蛋白，如轉錄因子及轉譯後修飾作用蛋白等，探討其共同調控基因表現的方式。若能將這些互作蛋白與HDAs的結構解析出來，對於表觀遺傳研究，將會是一項重大的突破。

3.藥物設計與開發： MTH1之抑制劑結構及其抑制效率分析
MutT Homolog 1 (MTH1)已被證實具有水解氧化的核甘三磷酸(nucleotide triphosphates, dNTPs)，以避免錯誤的核甘併入DNA複製，造成基因突變。在癌細胞中，容易產生高量的過氧化物，造成DNA損壞，MTH1則可藉由移除氧化的dNTP，以避免癌細胞進入細胞凋亡的程序。MTH1在正常細胞中表現量少，而在癌細胞中則會大量表現，因此抑制MTH1活性，將可能作為抑制癌細胞的藥物，促使癌細胞進入細胞凋亡。本研究與藥學系合作開發，初期共同篩選2300多筆片段化合物(fragment based compound library)，利用中研院超高速藥物篩選系統(ultra high throughput drug system)，找到4個化合物具有MTH1抑制能力，我們分析了這4個化合物的IC50及酵素動力學，並解出其中3個化合物與MTH1的蛋白質結構，未來將以這3個化合物結構為基礎，進一步設計新的化合物，分析MTH1抑制效率及對癌細胞生長的影響，這些結果將可提供有價值的藥物設計開發，並測試在動物系統的實驗成效。

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  • Ipomoelin - 甘藷葉中受創傷及Jasmonate誘導之糖結合蛋白

Lectin在植物中為一群糖結合蛋白的超級家族(superfamily)，當植物在遭受生物逆境時，如食草動物啃食造成創傷時，會大量表現這類蛋白，因此被視為植物在遭受動物取食時所產生的防禦性蛋白之一。 Ipomoelin(IPO)來自於甘藷(sweet potato)，在甘藷受蟲害侵擾時，大量表現於葉部。在經分析後，可被歸類為一群糖結合蛋白，稱為Jacalin-related Lectin，這群在結構上由單一蛋白摺疊成一個beta-三稜形(beta-prism)單體，再進一步組成四合體(tetramer)。 目前已知這群Jacalin-related Lectin具有結構多樣性的特徵，意思是指這群蛋白由相似的三稜形單體，可組成不同形式的雙體(dimer)、四合體(tetramer)、六合體(hexamer)及八合體(octomer)等。 
IPO在經過結構解析後，發現它具有額外的N端構造，可形成較緊密的四合體，此與目前在Jacalin這群所形成的四合體不太相同，雖然它們都由beta-三稜形的單體所組成，但在組合上卻甚為多變，這種多變性可提供蛋白質交互作用(Protein-protein interaction)的有用訊息。 另外，我們亦將methyl-alpha-D-mannose、methyl-alpha-D-glucose和(唾液酸)sialic acid等醣類，與IPO共結晶，取得複合體結構，經比較這些糖的結合模式，可以提供IPO對糖類結合的特異性，將有助這類糖結合蛋白在糖蛋白分析上的運用。PLoS ONE (2012) 7: e40618. Epub on Jul 11, 2012

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  • 植物抗蟲及抗菌之蛋白-半胱胺酸蛋白酶抑制劑之結構分析​​

Tarocystatin為一半胱胺酸蛋白酶抑制劑的一種，為芋頭中大量表達的一種蛋白酶抑制劑，目前針對此類蛋白酶抑制劑的研究，主要在於其對應蛋白酶(如木瓜酶papain)的抑制活性分析。由於真菌、線蟲及昆蟲等攝取植物，需經半胱胺酸蛋白酶的作用，因此植物藉由大量的蛋白酶抑制劑來達成減少或避免這些生物的入侵。 我們將Tarocystatin與木瓜酶共結晶，並以x光晶體繞射技術分析這個複合體結構，確立其蛋白酶抑制模式與動物中之結合模式類似，顯示在演化的過程中，這類半胱酸蛋白酶抑制劑是以類似的結構來達成植物抗蟲目的。除此之外，我們亦藉由抑制活性分析來完成Tarocystatin之抑制能力分析，接下來我們將目標放在C端結構。 

Tarocystatin屬植物半胱胺酸蛋白酶抑制劑(Phytocystatins)家族，本家族依分子量可分為三群：第一群分子量最小，約100個胺基酸具有單一CY domain，以水稻OC-1為代表，其蛋白質結構，以NMR方法於2000年解出，由Nagata等人發表於Biochemistry;第二群分子量較大，約205-250個胺基酸，以Tarocystatin為代表，可分為二個domain，一為與第一群序列相似的N端，為主要抑制區域，另一個C端延伸區，可能具有類似CY　domain結構，不具抑制功能。第三群為重覆CY domain所組成的蛋白酶抑制劑，具有約750個胺基酸有6~8個CY domain，以馬鈴薯(Potato)PMC為代表，其結構由Nissen等人發表於今年Plant cell(2009)。

在此我們的研究重點在第二群的Tarocystatin，此一特色在於本蛋白多了一段C端的CY-like domain，並不具有抑制劑的功能，因此我們嘗試將Tarocystatin與papain共結晶，希望能夠解出全長的Tarocystatin與papain的晶體結構，這將是Phytocystatins與papain的第一個複合體結構，同時也能提供重要的分子演化訊息。由於與具有活性的木瓜酶共結晶有其困難度，根據之前文獻指出，在許多狀況之下，僅有木瓜酶結構能被解析出來，雖然如此，我們仍嘗試進行其複合結構試驗。

在經過二年不斷蛋白質表達、純化、共結晶條件篩選之後，終於在一特定結晶條件，經一個月長出複合體晶體，經以同步輻射繞射分析後，取得解析度2.03Å的複合體結構，有趣的是，僅有N端CY domain與木瓜酶以1:1的方式結合，C端結構則無法被觀察到，此現象似乎意味著，C端的可能先與木瓜酶結合，以提高其N端的抑制能力。另外，我們亦設計不同片段，如全長、N端與C端及與GST結合與否，測試N端與C端的結合能力，經以Glutaraldehyde cross-linking 及yeast two hybrid 試驗分析，顯示Tarycystatin絕大部分為N端與C端分離的；少部分可以形成分子內結合；另外，亦有一部分可以透過N端與N端的結合，形成homodimer。最後我們亦測試其抑制能力的差異，結果發現GST-FL抑制木瓜酶的能力最好，GST-Nt 與FL次之，Nt抑制能力在這裏則是最弱，另外，GST-Ct則有促進木瓜酶活性的能力。由此結果表示Ct的出現對於提高抑制能力是相當重要的。 Planta. (2011) 234(2):243-54.Epub on Mar 17, 2011

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  • 植物在遭受非生物(缺水)逆境時，葉綠體中大量表現的抗逆境蛋白TLP18.3之結構與功能分析

關於TLP18.3之研究報告相當的少，在經剔除(knock out)實驗中，沒有明顯外表型出現，顯示其可能有類似蛋白同時存在葉綠體內，執行相似作用，顯示其重要性。根據推測TLP18.3可能參與光合系統II(PSII)的光修復作用，由於光合系統在長時間作用下，其D1蛋白易受光的破壞，此時即需要週邊蛋白來協助移除受損蛋白，此時TLP18.3即有可能執行此一重要任務，惟其分子功能並不清楚!因此本研究即是利用結構與功能的相關性，嘗試以X光晶體繞射研究，解析其結構，並藉由結構比對找出其可能之分子功能。 
由於TLP18.3蛋白不具甲硫胺酸，因此前二年即針對本蛋白的表達、純化、定點突變，進行許多測試，並分別取得native TLP18.3高解析繞射數據(解析度達1.52Å)，及運用TLP18.3突變體(解析度2.6Å)，以單波長不尋常散射法(SAD)取得相角後，運用建模軟體及修正程式完成蛋白質結構解析。在經結構比對後，幾個相近的結構具有酸性磷解酶活性，因此推測此一蛋白可能具有類似磷解酶活性，進一步設計活性分析，以受質pNPP進行序列酵素濃度、pH值、溫度、去除結合離子實驗，顯示其確實具有磷解酶活性功能。TLP18.3僅具有單一Domain，屬未知的家族DUF477(pfam)，在光合菌、藻類、植物及原核生物中，皆具有類似的蛋白，預計此一高解析的蛋白質結構將能提供這個家族的重要結構與功能資訊。 Plant Physiol. (2011) 157(3):1015-25 Epub on Sep 9, 2011

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尚有其他不同蛋白質相關研究及生物資訊分析 - Homology Modeling, Protein – Protein Docking, Molecular Dynamics and Simulation 等，歡迎對蛋白質表現、純化、結晶、X-ray 繞射、結構分析及蛋白質功能研究的大學部、碩士生、博士生加入本研究室，一起遨遊巨分子立體世界。 
更多相關研究訊息，請參閱本實驗室網頁。 

發表著作

(A) 學術期刊論文

  1. Hsin KT, Lee YH, Lin KC, Chen W, Cheng YS*. Specific binding between Arabidopsis thaliana phytochrome-interacting factor 3 (AtPIF3) bHLH and G-box originated prior to embryophyte emergence. BMC Plant Biol. 2024, Nov;  24:1060. doi: 10.1186/s12870-024-05777-z.

  2. Shih YH, Hung FY, Lin PY, Chen JS, Cheng YS, Yang S, Wu K*. Lysine acetylation regulates the subcellular localization and function of WRKY63.Plant Physiol. 2024 Sep 17:kiae492. doi: 10.1093/plphys/kiae492.

  3. Su GM, Chu LW, Chien CC, Liao PS, Chiu YC, Chang CH, Chu TH, Li CH, Wu CS, Wang JF, Cheng YS, Chang CH, Cheng CP*. Tomato NADPH oxidase SlWfi1 interacts with the effector protein RipBJ of Ralstonia solanacearum to mediate host defence. Plant Cell Environ. 2024 Dec;47(12):5007-5020. doi: 10.1111/pce.15086.

  4. Hung, F.Y., Feng, Y.R., Hsin, K.T., Shih, Y.H., Chang, C.H., Zhong, W., Lai, Y.C., Xu, Y., Yang, S., Sugimoto, K., Cheng, Y.S., Wu, K.* (2023) Arabidopsis histone H3 lysine 9 methyltransferases KYP/SUVH5/6 are involved in leaf development by interacting with AS1-AS2 to repress KNAT1 and KNAT2. Commun. Biol., 6:219.

  5. Hsin, K.T., Kuo, H.C., Kokubugata, G., Möller, M., Wang, C.N.*, Cheng, Y.S.* (2022) Allopatric Lineage Divergence of the East Asian Endemic Herb Conandron ramondioides Inferred from Low-Copy Nuclear and Plastid Markers. Int. J. Mol. Sci. 23:14932.

  6. Hsin, K.T., Hsieh, M.C., Lee, Y.H., Lin, K.C., Cheng, Y.S.* (2022) Insight into the Phylogeny and Binding Ability of WRKY Transcription Factors. Int. J. Mol. Sci. 23:2895. doi: 10.3390/ijms23052895

  7. Hsin, K.T., Wang, C.N., Cheng, Y.S.* (2021). Screening Three Single-copy Nuclear Markers to Infer Population Divergence in Conandron ramondioides (Gesneriaceae). J. Nat. Taiwan Museum, 74:15-25. doi: 10.6532/JNTM.202112_74(4).02

  8. Hsin, K.T., Yang, T.J., Lee, Y.H. and Cheng, Y.S.* (2021) Phylogenetic and Structural Analysis of NIN-Like Proteins With a Type I/II PB1 Domain That Regulates Oligomerization for Nitrate Response. Front. Plant Sci. 12:672035. doi: 10.3389/fpls.2021.672035.

  9. Li, L., Li, W., Gong, J., Xu, Y., Wu, Z., Jiang, Z., Cheng, Y.S., Li, Q., Ni, H.* (2021) An effective computational-screening strategy for simultaneously improving both catalytic activity and thermostability of α-L-rhamnosidase. Biotechnol Bioeng. 2021 Mar 20. doi: 10.1002/bit.27758.

  10. Peng C., Li, Y.H., Yu, C.W., Cheng, Z.H., Liu, J.R., Hsu, J.L., Hsin, L.W., Huang, C.T., Juan, H.F., Chern, J.W., Cheng, Y.S.* (2021) Inhibitor development of MTH1 via high-throughput screening with fragment based library and MTH1 substrate binding cavity. Bioorg Chem. 2021 Mar 10;110:104813. doi: 10.1016/j.bioorg.2021.104813.

  11. He, M.Y., Lin, Y.J., Kao, Y.L., Kuo, P., Grauffel, C., Lim, C., Cheng, Y.S., Chou, H.D.* (2021) Sensitive and Specific Cadmium Biosensor Developed by Reconfiguring Metal Transport and Leveraging Natural Gene Repositories. ACS Sens. 6:995-1002. doi: 10.1021/acssensors.0c02204.

  12. Chen, C.Y., Tu, Y.T., Hsu, J.C., Hung, H.C., Liu, T.C., Lee, Y.H., Chou, C.C., Cheng, Y.S.* and Wu, K.* (2020). Structure of Arabidopsis HISTONE DEACETYLASE15. Plant Physiol. 184:1585-1600.

  13. Chen, C.Y., Lin, P.H., Chen, K.H. and Cheng, Y.S.* (2020) Structural insights into Arabidopsis ethylene response factor 96 with an extended N-terminal binding to GCC box. Plant Mol. Biol., 104:483-498.

  14. Li, L.J., Tan, W.S., Li, W.J., Zhu, Y.B., Cheng, Y.S. and Ni, H.* (2019). Citrus Taste Modification Potentials by Genetic Engineering. Int. J. Mol. Sci., 20(24), 6194.

  15. Huang, H.Y. and Cheng, Y.S.* (2019). Heterologous overexpression, purification and functional analysis of plant cellulose synthase from green bamboo. Plant Methods, 15:80.

  16. Li, L., Gong, J., Wang, S., Li, G., Gao, T., Jiang, Z., Cheng, Y.S., Ni, H.*, and Li, Q. (2019). Heterologous Expression and Characterization of a New Clade of Aspergillus α-L-Rhamnosidase Suitable for Citrus Juice Processing. J. Agr. Food. Chem., 67(10), 2926-2935.

  17. Yu, C.W., Hung, P.Y., Yang, H.T., Ho, Y.H., Lai, H.Y., Cheng, Y.S.*, and Chern, J.W.* (2019). Quinazolin-2,4-dione-Based Hydroxamic Acids as Selective Histone Deacetylase-6 Inhibitors for Treatment of Non-Small-Cell Lung Cancer. J. Med. Chem., 62(2):857-874.

  18. Hsieh, H.C. and Cheng, Y.S.* (2018). Structural and thermondynamics analysis of Ipomoelin with metal ions show the metal-binding ability in Jacalin-related lectin. J. Nat. Taiwan Museum, 71:35-52.

  19. Ho, Y.H., Wang, K.J., Hung, P.Y., Cheng, Y.S., Liu, J.R., Fung, S.T., Liang, P.H., Chern, J.W.* and Yu, C.W.* (2018). A highly HDAC6-selective inhibitor acts as a fluorescent probe. Org. Biomol. Chem., 16, 7820-7832.

  20. Yu, C.W., Tai, R., Wang, S.C., Yang, P., Luo, M., Yang, S., Cheng, K., Wang, W.C. Cheng Y.S., Wu, K.* (2017) HISTONE DEACETYLASE6 Acts in Concert with Histone Methyltransferases SUVH4, SUVH5, and SUVH6 to Regulate Transposon Silencing. Plant Cell. 29: 1970-1983 Epub on Aug 4, 2017

  21. Chen, C.Y., Ho, S.S., Kuo, T.Y., Hsieh, H.L., Cheng Y.S.* (2017) Structural basis of jasmonate-amido synthetase FIN219 in complex with glutathione S-transferase FIP1 during the JA signal regulation. Proc. Natl. Acad. Sci. U.S.A. 114:E1815-E1824. Epub Feb 21, 2017

  22. Chen, H.Y., Cheng Y.S., Shih, H.H.* (2015) Expression patterns and structural modelling of Hsp70 and Hsp90 in a fish-borne zoonotic nematode Anisakis pegreffii. Vet Parasitol. 212:281-91. Epub on Jul 9, 2015.

  23. Chen, H.Y., Cheng Y.S., Grabner, D.S., Chang S.H. and Shih, H.H.* (2014) Effect of different temperatures on the expression of the newly characterized heat shock protein 90 (Hsp90) in L3 of Anisakis spp. isolated from Scomber australasicus. Vet Parasitol. 205:540-550. Epub on Sep 13, 2014.

  24. Wu H.Y. and Cheng Y.S.* (2014) Combining secondary-structure and protein solvent-accessibility predictions in methionine substitution for anomalous dispersion. Acta Crystallogr F Struct Biol Commun. 70:378-83. Epub on Fed 19, 2014.

  25. Yang, W.C.; Lin, Y.M., Cheng, Y.S. and Cheng, C.P.* (2013) Ralstonia solanacearum RSc0411 (lptC) is a determinant for full virulence and has a strain-specific essential function in the T3SS activity. Microbiology. 159:1136-48. Epub on Mar 21, 2013.

  26. Chang, W.C., Liu, K.L., Hsu, F.C., Jeng, S.T. and Cheng, Y.S.* (2012) Ipomoelin, a Jacalin-related lectin with a compact tetrameric association and versatile carbohydrate binding properties regulated by its N terminus. PLoS ONE 7: e40618. Epub on Jul 11, 2012

  27. Wu, H.Y., Liu, M.S., Lin, T.P. and Cheng, Y.S.* (2011) Structural and functional assays of AtTLP18.3 Identify its novel acid phosphatase activity in thylakoid lumen. Plant Physiol. 157(3):1015-25 Epub on Sep 9, 2011

  28. Chu, M.H., Liu, K.L., Wu, H.Y., Yeh, K.W. and Cheng, Y.S.* (2011) Crystal structure of tarocystatin-papain complex: implications for the inhibition property of group-2 phytocystatins. Planta. 234(2):243-54.Epub on Mar 17, 2011

  29. Chu, W.Y., Huang Y.F., Huang C.C., Cheng, Y.S., Huang C.K. and Oyang Y.J. (2009) ProteDNA: a sequence-based predictor of sequence-specific DNA-binding residues in transcription factors. Nucl. Acids Res. 37 (Web Server issue):W396-401.Epub on May 29, 2009

  30. Wang, K.M., Rajendran, S.K., Cheng, Y.S., Venkatagiri, S, Yang, A.H., Yeh, K.W. (2008) Characterization of inhibitory mechanism and antifungal activity between group-1 and group-2 phytocystatin from taro (Colocasia esculenta) FEBS J. 275(20):4980-9.Epub on Sep 10, 2008

  31. Lai, C.K., Jeng, K.S., Machida, K., Cheng, Y.S., and Lai, M.M. (2008) Hepatitis C virus NS3/4A protein interacts with ATM, impairs DNA repair and enhances sensitivity to ionizing radiation. Virology. 2008 Jan 20;370(2):295-309. Epub on Oct 10, 2007

  32. Shen, S.T., Cheng, Y.S., Shen, T.Y., and Yu, J.Y.L. (2006) Molecular cloning of follicle-stimulating hormone beta-subunit cDNA from duck pituitary. Gen. Comp. Endocrinol. 148:388-94.

  33. Cheng, Y.S., Doudeva, L.G., Yang, W.Z., Hsia, K.C., Shi, Z., Chak K.F. and Yuan, H.S. (2006) High-resolution crystal structure of ColE7 translocation domain: Implications for transport across membranes. J. Mol. Biol. 356:22-31

  34. Doudeva, L.G., Huang, H.C., Hsia, K.C., Shi, Z.G., Li, C.L., Shen, Y.L., Cheng, Y.S. and Yuan H.S. (2006) How a His-metal finger endonuclease ColE7 binds and cleaves DNA with a transition metal ion cofactor. Protein Science 15:269-280

  35. Tsai, L.C., Shyur L.F., Cheng, Y.S. and Lee, S.H.(2005) Crystal Structure of Truncated Fibrobacter succinogenes 1,3-1,4-β-D-Glucanase in Complex with β-1,3-1,4-Cellotriose. J. Mol. Biol., 354:642-651

  36. Liu, H., Peng, H.H., Cheng, Y.S., Yuan, H.S. and Yang-Yen H.F. (2005) Stabilization and Enhancement of the anti-apoptotic activity of Mcl1 by TCTP. Mol. Cell. Biol. 25:3117-3126

  37. Hsia, K.C., Chak, K.F., Liang, P.H., Cheng, Y.S., Ku, W.Y. and Yuan, H.S. (2004) DNA binding and degradation by the H-N-H protein ColE7. Structure, 12:205-214.

  38. Cheng, Y.S., Hsia, K.C., Doudeva, L.G. and Yuan, H.S. (2002) The crystal structure of the nuclease domain of colicin E7 suggests a mechanism for binding to double-stranded DNA by the H-N-H endonucleases. J. Mol. Biol. 324:227-236.

  39. Cheng, Y.S., Yang, W.Z., Johnson, R.S. and Yuan, H.S. (2000) Structural Analysis of the Transcriptional Activation Region on Fis: Crystal Structures of Six Fis Mutants with Different Activation Properties. J. Mol. Biol. 302:1139-1151.

  40. Cheng, Y.S., Tang, T.K. and Hwang, M.J. (1999) Amino acid conservation and clinical severity of human glucose-6-phosphate dehydrogenase mutations. J. Biomed. Sci. 6:106-114

  41. Cheng, Y.S.; Lin, C.H. and Chen, L.J. (1997) Transcription and processing of the gene for spinach chloroplast threonine tRNA in a homologous in vitro system. Biochem. Biophys. Res Commun. 233:380-385

​​

(B) 研討會論文

  1. Yi-Sheng Cheng. (2024, May) Molecular interplay of HDA15, WRKY63, and FLC W-box in regulating flowering time. The joint symposium of the Taiwan biophysical society and international network of protein engineering centers. National Synchrotron Radiation Research Center (NSRRC). May 22-25, 2024 (Invited Speaker)

  2. Wei-Bin Wu and Yi-Sheng Cheng. (2024, May) Selective Inhibitor Development of Human Histone Deacetylase 7. The joint symposium of the Taiwan biophysical society and international network of protein engineering centers. National Synchrotron Radiation Research Center (NSRRC). May 22-25, 2024

  3. 鄭貽生 (2023, Dec) 植物抗蟲抗菌的防禦蛋白 輔仁大學生命科學系

  4. Yen-Hua Chang, Yi-Sheng Cheng (2022, Nov) Heterogeneous Expression, Purification and Inhibitor Development of Histone Deacetylase 10. 2022 TSBMB Autumn Camp, The frontiers of biochemistry in Biomedical Science. 麻布山林，新竹縣北埔鄉

  5. Jian-sheng Chen, Yi-Sheng Cheng (2022, Oct) Interplay between WRYKY63 and HDA15 in regulation of gene expression of stress responses. 2022 post-pandemic era for frontier plant science and sustainable agriculture conference, 惠蓀林場，南投

  6. Kuan-Ting Hsin, Hao-Chih Kuo, Goro Kokubugata, Michael Möller, Chun-Neng Wang, Yi-Sheng Cheng (2022, Oct) Allopatric lineage divergence of an East Asia endemic herb Conandron ramondioides inferred from low copy nuclear and plastid markers. 2022 post-pandemic era for frontier plant science and sustainable agriculture conference, 惠蓀林場，南投

  7. Ting-Yi Yu, Yi-Sheng Cheng, Hsin-Hung Yeh (2022, Jun) Functional analysis between AtSAP5 and AtTrx3 in the reduced salicylic acid immunity pathway. ABA, APPA and TBS Joint Congress, National Cheng Kung University, International Conference Center.

  8. Yi-Sheng Cheng (2019). Heterologous overexpression, purification and functional analysis of cellulose synthases from green bamboo. 第七屆海峽兩岸植物科學與農業生物技術研討會暨2019年廣東省植物生理學會學術年會, 廣東茂名.

  9. Chia-Yang Chen, Yi-Tsung Tu, Yi-Sheng Cheng, and Keqiang Wu (2019). The structure and activity of Arabidopsis histone heacetylase 15 are regulated by oligomerization and phosphorylation. 2019 TSPB Annual meeting & Symposium, International Conference Hall, Academica Sinica, Taipei, Taiwan.

  10. Yi-Sheng Cheng (2019). Structural and functional analyses reveal Histone Deacetylase 15 regulated by oligomerization and phosphorylation in Arabidopsis. Japan-Taiwan Plant Biology 2019, 日本名古屋大學.

  11. Yi-Sheng Cheng (2018). Structural and functional analyses reveal Histone Deacetylase 15 regulated by oligomerization and phosphorylation in Arabidopsis. 2018 International Symposium on Plant and Environment Interaction, Conference room R332, Life Science Building, NTU.

  12. Yi-Sheng Cheng (2018). Structural basis of jasmonate-amido synthetase FIN219 in complex with glutathione S-transferase FIP1 during the JA signal regulation. NTU-CUHK 植物科學研討會, 台大管理學院一號館.

  13. Hsuan-Yu Huang and Yi-Sheng Cheng* (2018). Heterologous overexpression, purification and functional analysis of cellulose synthases from green bamboo. 第23屆生物物理研討會, 國立中興大學圖書館7樓國際會議廳.

  14. Ting-Chun Liu and Yi-Sheng Cheng* (2018). Development of Ipomoelin as an affinity tag in recombinant protein expression and purification. 第23屆生物物理研討會, 國立中興大學圖書館7樓國際會議廳.

  15. Yu-Hsuan Lee and Yi-Sheng Cheng* (2018). Structure based drug development for MutT homolog 1. 第23屆生物物理研討會, 國立中興大學圖書館7樓國際會議廳.

  16. Yi-Sheng Cheng (2018). Structural basis of Jasmonate-amido Synthetase FIN219 in complex with glutathione S-transferase FIP1 during the JA signal regulation. 廈門集美大學食品與生物工程學院, 廈門集美大學.

  17. Yi-Sheng Cheng (2018). Structural basis of Jasmonate-amido Synthetase FIN219 in complex with glutathione S-transferase FIP1 during the JA signal regulation. 結晶學小型研討會, 台灣大學化學系B281會議室.

  18. Yi-Sheng Cheng (2017) Dissecting molecular function of Arabidopsis Histone Deacetylase 15. Invited Speaker, 2017Taiwan-Japan Plant Biology2017. Humanities and Social Sciences Building, Academia Sinica. Nov. 3-6.

  19. Cheng Peng and Yi-Sheng Cheng (2017) Structure based inhibitor development for MutT Homolog 1. 第22屆生物物理研討會, 義守大學行政大樓十樓 國際演講廳. May, 17-19 *本文榮獲第22屆生物物理研討會壁報論文競賽第二名

  20. Pei-Wen Liao, Heng-Chen Hung and Yi-Sheng Cheng (2017) Enzymatic Activity and Oligomerization of Histone Deacetylase 15 Regulated by Phosphorylation. 第22屆生物物理研討會, 義守大學行政大樓十樓 國際演講廳. May, 17-19; 植科所105學年科學論文壁報競賽

  21. Min-Che Hsieh and Yi-Sheng Cheng (2016) The Mechanisms of Arabidopsis WRKY54 DNA binding Domain to W boxes. 第21屆生物物理研討會, 國立清華大學生命科學系. May, 19-21; 植科所104學年科學論文壁報競賽, June, 3

  22. Kun-Hong Chen and Yi-Sheng Cheng (2016) Structural and functional analyses of ERF19 in response to biotic stresses. 第21屆生物物理研討會, 國立清華大學生命科學系. May, 19-21; ; 植科所104學年科學論文壁報競賽, June, 3

  23. Jhe-Cheng Hsu and Yi-Sheng Cheng (2016) Characterization of Arabidopsis histone deacetylase 15. 第21屆生物物理研討會, 國立清華大學生命科學系. May, 19-21; ; 植科所104學年科學論文壁報競賽優選獎, June, 3

  24. Hsuan-Yu Huang and Yi-Sheng Cheng (2016) Heterologous overexpression and purification of plant celluloase synthase from Bambusa oldhamii. 第21屆生物物理研討會, 國立清華大學生命科學系. May, 19-21; ; 植科所104學年科學論文壁報競賽, June, 3

  25. Yi-Sheng Cheng (2015) Structural and biochemical analyses of Arabidopsis HDA5 reveal the regulation of histone deacetylase activity. Invited Speaker, 第六屆海峽兩岸植物科學暨農業生物技術研討會 廣東, 廣州 Dec, 3-7

  26. Yi-Sheng Cheng (2015) Biochemical Assays and EM Structure of the Class II of AtHDA5. Invited Speaker, 第十二屆海峽兩岸電子顯微鏡研討會 四川, 稻城 Sep, 6-11

  27. Yi-Sheng Cheng (2015) Structure insights into FIN219-FIP1 complex. Invited Speaker, Workshop of Zentrum für Molekularbiologie der Pflanzen (ZMBP), Tübigen University, Germany. July, 13-15

  28. Yi-Jui Chen, Ready Tai, Keqiang Wu, and Yi-Sheng Cheng (2015) Structural and Biochemical Assays of ClassII AtHDA5. 26th International Conference on Arabidopsis Research (ICAR), Paris, French. July, 5-9

  29. Han-Chen Hsieh and Yi-Sheng Cheng (2015) Structural and thermodynamic analysis of Ipomoelin in complex with metals reveal its metal binding properties. 植科所103學年科學論文壁報競賽優等獎. Jun 5.

  30. Wei Chen and Yi-Sheng Cheng (2015) Study on bHLH domain from Arabidopsis PIF3 binding to G-Box DNA. 第20屆生物物理研討會, 中央研究院生物化學研究所. May, 11-13; 植科所103學年科學論文壁報競賽優等獎 Jun 5.

  31. Pei-Husan Lin and Yi-Sheng Cheng (2015) DNA Binding Assays of ERF96 with GCC boxes. 第20屆生物物理研討會, 中央研究院生物化學研究所. May, 11-13; 植科所103學年科學論文壁報競賽佳作Jun 5.

  32. Chun-Yen Chen, Hsu-Liang Hsieh and Yi-Sheng Cheng (2015) Mechanistic insights into structure of FIN219-FIP1 complex. 第20屆生物物理研討會, 中央研究院生物化學研究所. May, 11-13

  33. Tzu-Jing Yang and Yi-Sheng Cheng (2015) Molecular basis for oligomerization of nitrate response regulator AtNLP7. 第20屆生物物理研討會, 中央研究院生物化學研究所. May, 11-13; 植科所103學年科學論文壁報競賽優等獎 Jun 5.

  34. Yi-Sheng Cheng (2014) Molecular structure and function of Ipomoelin in oligomerization for its antibacterial and insecticidal ability. 中央研究院南部研究中心邀請演講 楊祥發講堂. Oct, 22

  35. Yi-Sheng Cheng (2014) Exploring the Polymer Form of Arabidopsis Histone Deacetylase 6 by Electron Microscopy to Reveal Its Composition. 臺灣顯微鏡學會第三十四屆學術研討會暨第十一屆海峽兩岸電子顯微鏡學術研討會, 臺灣大學應用力學館國際會議廳. Jun, 23-24

  36. Yi-Sheng Cheng (2014) 抗蟲抗菌的植物凝集素植物的逆轉生存之道. 臺北市建國中學生物研習, May, 20.

  37. Hsing-Yi Lai and Yi-Sheng Cheng (2014) Study on the binding modes between hHDAC6 and its inhibitors. The 19th Biophysics Conference, 國立成功大學 光復校區 學生活動中心多功能廳與國際會議廳 May, 7-10

  38. Yi-Jui Chen, Ready Tai, Keqiang Wu, and Yi-Sheng Cheng (2014) Plant HDA5 shows a large polysome with histone deacetylase activity. The 19th Biophysics Conference, 國立成功大學 光復校區 學生活動中心多功能廳與國際會議廳 May, 7-10

  39. Han-Chen Hsieh, Rong-Huay Juang and Yi-Sheng Cheng (2014) Oligomeric states of AtPCS1 by biophysical analyses show its nonspecific association. The 19th Biophysics Conference, 國立成功大學 光復校區 學生活動中心多功能廳與國際會議廳 May, 7-10

  40. Wen-Jiun Wang and Yi-Sheng Cheng (2014) Structural and Functional Studies For Arabidopsis Histone Deacetylase 6. The 19th Biophysics Conference, 國立成功大學 光復校區 學生活動中心多功能廳與國際會議廳 May, 7-10

  41. Chia-Yu Chien and Yi-Sheng Cheng (2014) Structural and Biophysical Analyses of Arabidopsis PIF3 basic helix-loop-helix Domain binding to e-box DNA. For Arabidopsis Histone Deacetylase 6. The 19th Biophysics Conference, 國立成功大學 光復校區 學生活動中心多功能廳與國際會議廳 May, 7-10

  42. Yi-Sheng Cheng (2013) Molecular structure and function of Ipomoelin in oligomerization for its antibacterial and insecticidal ability. 中央研究院細胞與個體生物學研究所"國立台灣大學生命科學系學術檢討會, 台大生科館3樓演講廳， Oct, 8-9.

  43. Hsin-Yi Wu, Tsan-Piao Lin, and Yi-Sheng Cheng (2013) Structural and Functional Assay of AtTLP18.3 revealed its novel phosphatase activity involved in Repair Cycle of Photosystem. 植科所101學年科學論文壁報競賽佳作, 台大體育館， Jun, 7.

  44. Yung-Chi Huang, Shih-Tong Jeng, Yi-Sheng Cheng (2013) Molecular Function of Ipomoelin in Oligomerization for Their Antibacterial and Insecticidal Ability. 植科所101學年科學論文壁報競賽優等獎, 台大體育館, Jun, 7.

  45. Yi-Sheng Cheng (2012) Expression and purification strategies of recombinant proteins for further related applications. 國防醫學院預防醫學研究所，三峽, Nov, 30.

  46. Yi-Sheng Cheng (2012) Protein structures of Epigenetic regulating proteins. 清华大学与台湾大学合作交流学术报告会, 清华大学生命科学新馆143会议室, June, 26.

  47. Kai-Wen Fan, Kai-Wun Yeh, Yi-Sheng Cheng (2012) Monomeric and Dimeric Form of Tarocystatin Showed Different Binding Property to Papain. The 17th Biophysics Conference, Institute of BioMedical Sciences, Academia Sinica; 植科所100學年科學論文壁報競賽佳作

  48. Chun-Yen Chen, Yi-Sheng Cheng (2012) Determination of protein interaction and enzymatic kinetics between FIN219/JAR1 and Glutathione S-Transferases using Quartz Crystal Microbalance. The 17th Biophysics Conference, Institute of BioMedical Sciences, Academia Sinica

  49. Wei-Chieh Chang, Kai-Lun Liu, Shih-Tong Jeng, Fang-Ciao Hsu and Yi-Sheng Cheng (2011) Ipomoelin, a member of Jacalin-related Lectin with a different tetrameric association and versatile carbohydrate binding properties regulating by its N terminus. 第二届海峡两岸植物科学暨农业生物技术研讨会, 中山大學, 廣州

  50. Wei-Chieh Chang, Shih-Tong Jeng and Yi-Sheng Cheng (2011) Quaternary structure and energetic analysis of ipomoelin in complex with various carbohydrates for exploring its binding diversity. The 16th Biophysics conference, College of Sciences and Engineering, National Dong Hwa University, Taiwan

  51. Ming-Hung Chu, Kai-Lun Liu, Kai-Wun Yeh and Yi-Sheng Cheng (2009) Complex structure of tarocystatin-papain and characterization of tarocystatin proposed the roles of C-terminal extension in phytocystatins. Joint Conference of the Asian Crystallographic Association & Chinese Crystallography Society (AsCA'09) Beijing, China

  52. Hsin-Yi Wu, Mao-Sen Liu, Tsan-Piao Lin, and Yi-Sheng Cheng (2009) High-Resolution Crystal Structure and Functional Analysis of a Truncated Thylakoid Lumen Protein AtTLP18.3 Reveal its Novel Phosphatase Activity. Joint Conference of the Asian Crystallographic Association & Chinese Crystallography Society (AsCA'09) Beijing, China

  53. Kai-Lun Liu, Shih-Tong Jeng, and Yi-Sheng Cheng (2009) Crystal structures of Ipomoelin in complex with various carbohydrates, MMP, MGP and Sialic acid NSRRC Fifteenth User' Meeting, Hsinchu, Taiwan

  54. Hsin-Yi Wu, Mao-Sen Liu, Tsan-Piao Lin, and Yi-Sheng Cheng (2009) High-Resolution Crystal Structure and Functional Assay of a Truncated Thylakoid Lumen Protein AtTLP18.3 Reveal its Novel Phosphatase Activity. Joint International Conference of Biophysics and 14th Annual Conference of the Biophysical Society of ROC, NCKU, Tainan

  55. Ming-Hung Chu, Kai-Wun Yeh and Yi-Sheng Cheng (2009) Domain analysis of tarocystatin revealed the inhibitory property of group II phytocystatin. Joint International Conference of Biophysics and 14th Annual Conference of the Biophysical Society of ROC, NCKU, Tainan

  56. Sih-Syun Ho, Zhi-Gong Wang, Hsu-Liang Hsieh, and Yi-Sheng Cheng (2009) Purification and crystallization of FIN219-FIP1 complex and biochemical assay of FIN219. Joint International Conference of Biophysics and 14th Annual Conference of the Biophysical Society of ROC, NCKU, Tainan

  57. Yi-Sheng Cheng, Hsin-Yi Wu, Ming-Hung Chu, Kai-Wun Yeh (2008)Structural model for group-2 phytocystatin revealed the protein folds resembling to human latexin . 19th International Conference on Genome Informatics 2008, GIW2008, Australia

  58. Yi-Sheng Cheng (2008) Structural analysis of IL2-inducible T-cell kinase (ITK) in pedigree 135 mice. Symposium of the national research program for genomic medicine.

  59. Ke-Ming Wang, Shripathi Venkatagiri, Ai-Hwa Yang, Yi-Sheng Cheng* and Kai-Wun Yeh (2007) Structural model and inhibitory characteristics for group-2 phytocystatin from taro. Symposium on Frontiers of Plant Science. *Invited Speaker

  60. Kuo-Chiang Hsia, Kin-Fu Chak, Po-Huang Liang, Yi-Sheng Cheng, Wen-Yen Ku, and Hanna S. Yuan (2004) DNA Binding and Degradation by the HNH Protein ColE7. The 9th Symposium on Recent Advances in Biophysics.

  61. Nancy Yu, Yi-Sheng Cheng (2004) Codon Usage Enhancer (CUE): A JAVA-based Freeware for Manipulating Codon Usage. The 9th Symposium on Recent Advances in Biophysics.

  62. Kuo-Chiang Hsia, Kin-Fu Chak, Po-Huang Liang, Yi-Sheng Cheng, Wen-Yen Ku, and Hanna S.Yuan (2003) DNA Binding and Degradation by the HNH Protein ColE7. 第四屆東亞生物物理研討會

  63. 蔡麗珠，李淑華，鄭貽生，徐麗芬 (2003) 葡聚醣水解酶和三糖複合體晶體結構. 中國化學會92年年會

  64. Yi-Sheng Cheng, Wen-Yen Ku, Meng-Jiun Sui, Kuo-Chiang Hsia, Li-Chu Tsai, Jia-Lueng Li, Wei-Zeng Yang, Lyudmila G. Doudeva and Hanna S. Yuan (2002) Bacterial offense and defense mechanisms using nucleases. The 8th Symposium on Recent Advances in Biophysics.

  65. Yi-Sheng Cheng, Kuo-Chiang Hsia, Lyudmila G. Doudeva , and Hanna S. Yuan (2002) The crystal structure of the nuclease domain of colicin E7 suggests a mechanism for binding to double-stranded DNA by the HNH endonucleases. The 8th Symposium on Recent Advances in Biophysics.

  66. Meng-Jiun Sui, Li-Chu Tsai, Yi-Sheng Cheng, Ludmila Doudeva and Hanna S. Yuan (2001) The zinc ion in the HNH motif of colicin E7 plays a catalytic role. The 8th Symposium on Recent Advances in Biophysics.

  67. Yi-Sheng Cheng, Hanna S. Yuan (2000) Structural Analysis of the Transcriptional Activation Region on Fis: Crystal Structures of Six Fis Mutants with Different Activation Properties. The 6th Symposium on Recent Advances in Biophysics.

  68. Yi-Sheng Cheng, Ming-Jing Hwang (1998) Sequence Conservation in Three-dimensional Structure of Human G6PD and Its Mutants. 第六屆細胞及分子生物新知研討會

  69. Yi-Sheng Cheng, Ming-Jing Hwang (1998) A scheme for visualizing amino acid conservation and its structural context. XVIII international conference on magnetic resonance in biological systems.

  70. Yi-Sheng Cheng, Ming-Jing Hwang (1997) Computer modeling the substrate binding of glucose-6-phosphate dehydrogenase. The 3th Symposium on Recent Advances in Biophysics.

 (C) 專書及專書論文

  1. 鄭貽生 (2021) 代謝體學在植物次級代謝物之分析與運用. 林業研究專訊，28:5-9 

  2. Chen H.Y., Cheng Y.S., Shih H.H.* (2018) Heat Shock Proteins: Role, Functions and Structure in Parasitic Helminths. Chapter 12 in Heat Shock Proteins in Veterinary Science, Heat Shock Proteins Book Series, ed. by A. A. Asea and P. Kaur, Springer International Publishers.

  3. 鄭貽生、蔡麗珠、楊維仁、袁小琀 (2003) 第七章 X光晶體繞射學與結構生物學 後基因體時代之生物技術 pp81-90

開設課程

  • B01 101B0_普通生物學乙上

  • B01 106B1_普通生物學實驗乙上

  • B01 101A1_普通生物學甲上

  • B01 106A1_普通生物學實驗甲上

  • B01 49100_專題研究

  • B42 M0020_專題研究

  • B42 D0020_專題研究

  • B42 M1510_植物科學特論

  • P05 U2020_生物技術核心實驗

  • B01 40010_書報討論(一)

  • B01 40020_書報討論(二)

  • B42 U1240_蛋白質體學

  • LS 7037_結構生物學專題討論

  • LS 1028_遺傳工程概論

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