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Lee CH, Shih YP, Ho MR, Wang AH*
Academician Andrew H.-J. Wang and his team at the Institute of Biological Chemistry have recently found that the C-terminal D/E-rich domain of MBD3 was able to associate with the Z-DNA binding domain (Zα) of ADAR1. The D/E-rich domain of MBD3 may act as a DNA mimic to compete with Z-DNA for binding to Zα. The interplay of MBD3 and ADAR1 may participate in regulating the local DNA conformational transition between B-DNA and Z-DNA and thereby results in alterations in gene expression. ... Read more

I-Ming Lee, Feng-Ling Yang, Te-Li, Chen, Kuo-Shiang Liao, Chien-Tai Ren, Nien-Tsung Lin, Yu-Pei Chang, Chung-Yi Wu* and Shih-Hsiung Wu*
Infection by antibiotic resistant bacterial pathogens poses a serious global health threat. Therefore, a new therapy is urgently required to overcome the failure of antibiotic. Glycoconjugate vaccine have been proven to be effective in combating a broad spectrum of diseases caused by antibiotic resistant bacteria, and was suggested as a promising solution. In this regard, ising the efficacy of ... Read more

Jeffy Chern, Chun-Ping Lu, Zhanxiong Fang, Ching-Ming Chang, Kuo-Feng Hua, Yi-Ting Chen, Cheng Yang Ng, Yi-Lin Sophia Chen, Yulin Lam*, and Shih-Hsiung Wu*
Traditional medicines provide a fertile ground to explore potent "lead" compounds with desired effects; yet, their transformation into modern drugs is often fraught with challenges in deciphering the target that is mechanistically valid for its biological activity. The research team led by Dr. Shih-Hsiung Wu, a Distinguished Research Fellow in the Institute of Biological Chemistry, and collaborators in National Ilan University and National University of Singapore determined the acting target and molecular mechanism of Z-(+)-isochaihulactone ... Read more


Ming-Yuan Su, Nilanjan Som, Chia-Yun Wu, Shih-Chieh Su, Yi-Ting Kuo, Lu-Chu Ke, Meng-Ru Ho, Shiou-Ru Tzeng, Ching-Hao Teng, Dominique Mengin-Lecreulx, Manjula Reddy & Chung-I Chang
A new structural study, published online on November 15 in Nature Communications, demonstrates how a lipoprotein adaptor and a protease form a three-sided docking cradle to mediate protein degradation in the E. coli outer membrane. The research team led by Dr. Chung-I Chang, Associate Research Fellow of the Institute of Biological Chemistry, has revealed the coordination between a homodimer of the lipoprotein adaptor NlpI and two molecules of the periplasmic PDZ-protease Prc by using X-ray crystallography, ... Read more

Wen-Jin Wu, Wei Yang & Ming-Daw Tsai
Academician Ming-Daw Tsai, a Distinguished Research Fellow, and Dr. Wen-Jin Wu, an Associate Research Specialist at the Institute of Biological Chemistry have published an invited review article entitled “How DNA polymerases catalyze replication and repair with contrasting fidelity” in Nature Reviews Chemistry on September 6th. This article has also been selected as the cover article in this issue.
“DNA polymerases were named for their function of catalyzing DNA replication, a process that is necessary for growth and propagation of life. ... Read more

Lai CY, Lo IW, Hewage RT, Chen YC, Chen CT, Lee CF, Lin S, Tang MC, Lin HC
In nature, living organisms use primary metabolites containing simple building blocks as their starting materials. An important part of utilizing these starting materials is enzymes, which efficiently catalyze a variety of chemical reactions and generate a large number of natural products through biosynthetic pathways. Because these natural products, or organic compounds, usually exhibit biological or pharmacological activity, they have been crucial in chemistry development and drug discovery. ... Read more

Ya-Ting Wang, Jocelyn Chen, Chou-Wei Chang, Jayu Jen, Tzu-Yu Huang, Chun-Ming Chen, Roger Shen, Suh-Yuen Liang, I-Cheng Cheng, Shuenn-Chen Yang, Wu-Wei Lai, Kuang-Hung Cheng, Tao-Shih Hsieh, Ming-Zong Lai, Hung-Chi Cheng, Yi-Ching Wang, Ruey-Hwa Chen
Recent advances in cancer biology have evolved to consider cancers as complex “rough” organs in which transformed cells along with other cell and non-cell constituents in the tumor microenvironment (TME) conspire to facilitate tumor growth and metastasis. ... Read more

Yu-Sung Cheng, Zih-ten Chen, Tai-Yan Liao, Chen Lin, Howard C.-H. Shen, Ya-Han Wang, Chi-Wei Chang, Ren-Shyan Liu, Rita P.-Y. Chen, Pang-hsien Tu
Dr. Rita P.-Y. Chen, an Associate Research Fellow at the Institute of Biological Chemistry along with Dr. Pang-hsien Tu, a former Assistant Research Fellow at the Institute of Biomedical Sciences, and their research teams recently found that a modified short peptide delays the onset of Alzheimer’s disease when delivered in the form of a nasal drop in a mouse model. The research was published in EMBO Molecular Medicine on March 29th, 2017. ... Read more


Po-Ting Chen, Zih-ten Chen, Wen-Chi Hou, Lung-Chih Yu, Rita P.-Y. Chen
Dr. Rita P.-Y. Chen and her research team at the Institute of Biological Chemistry has recently discovered that polyhydroxycurcuminoids, but not curcumin itself, may be useful in the prevention of Alzheimer’s disease. They found that these compounds upregulate neprilysin (NEP), the most important amyloid-β peptide (Aβ)-degrading enzyme. Many recent reports have shown that Aβ clearance is a promising strategy in preventing and treating Alzheimer’s disease, and NEP is the most important Aβ-degrading enzyme ... Read more

1. Chien-Chu Lin, Shih-Chieh Su, Ming-Yuan Su, Pi-Hui Liang, Chia-Cheng Feng, Shih-Hsiung Wu, Chung-I Chang
2. Shih-Chieh Su, Chien-Chu Lin, Hui-Chung Tai, Mu-Yueh Chang, Meng-Ru Ho, C. Satheesan Babu, Jiahn-Haur Liao,
    Shih-Hsiung Wu, Yuan-Chih Chang, Carmay Lim, Chung-I Chang
Though geographically compact, Taiwan is a hot spring of resources. In fact, researching “extreme” organisms from hot springs may help answer fundamental biological questions. This is beautifully illustrated in the work of the Taiwanese research team led by Dr. Chung-I Chang, investigating an energy-dependent proteolytic machine ... Read more

Chin-Chih Liu, Yu-Ching Lin, Yu-Hsuan Chen, Chun-Ming Chen, Liang-Yu Pang, Hsuan-An Chen, Pei-Rung Wu, Mei-Yao Lin, Si-Tse Jiang, Ting-Fen Tsai, and Ruey-Hwa Chen
A team led by Dr. Ruey-Hwa Chen, a Distinguished Research Fellow at the Institute of Biological Chemistry recently discovered that a KLHL20-based ubiquitin ligase controls the termination of autophagy. The research was published in the top molecular and cell biology journal Molecular Cell on December 10, 2015.
Autophagy is a cell self-eating process through which cellular components are delivered from ... Read more


Kai-En Chen, Shu-Yu Lin, Mei-Ju Wu, Meng-Ru Ho, Abirami Santhanam, Chia-Cheng Chou, Tzu-Ching Meng, Andrew H.-J. Wang
Ras signaling cascade has long been considered as an attractive therapeutic target for colorectal cancer (CRC) where PTPN3 is highly expressed and expected to promote Ras oncogenic signaling through dephosphorylation of fully activated p38γ. Recent attention has been drawn on the PDZ-mediated PTPN3-p38γ complex, which is known to be the novel target for Ras-dependent malignancies. However, the dynamic nature of the phosphatase-kinase interactions ... Read more

Wen-Jin Wu, Mei-I Su, Jian-Li Wu, Sandeep Kumar, Liang-hin Lim, Chun-Wei Eric Wang, Frank H. T. Nelissen, Ming-Chuan Chad Chen, Jurgen F. Doreleijers, Sybren S. Wijmenga, and Ming-Daw Tsai
Replication of DNA occurs in all living organisms and forms the basis of biological inheritance. Replication of DNA famously occurs through the pairing of the nucleic acid (base) building blocks of DNA in a specific pattern, (guanine pairs with cytosine and adenine pairs with thymine). This rule of base pairing is named Watson-Crick base pairing. The synthesis of new strands of DNA is facilitated by enzymes called DNA polymerases. For many years scientists ... Read more


Hong-Wen Tang, Hsiao-Man Liao, Wen-Hsin Peng, Hong-Ru Lin, Chun-Hong Chen, Guang-Chao Chen
Research team led by Dr. Guang-Chao Chen used fruit fly (Drosophila) adult midgut and mammalian cells to investigate the role of autophagy (degradation of cell superfluous cell components) under oxidative stress (a possible cause of many human diseases). They showed that autophagy not only degrades damaged organelles and proteins but, more importantly, plays an important role in maintaining tissue homeostasis by regulating stem cell proliferation and cell death in response to oxidative stress ... Read more

Yuan-Feng Lin, Tsung-Ching Lai, Chih-Kang Chang, Chi-Long Chen, Ming-Shyan Huang, Chih-Jen Yang, Hon-Ge Liu, Jhih-Jhong Dong, Yi-An Chou, Kuo-Hsun Teng, Shih-Hsun Chen, Wei-Ting Tian, Yi-Hua Jan, Michael Hsiao, and Po-Huang Liang
Research team led by Dr. Po-Huang Liang has identified a small-molecule inhibitor I-Lys, which can activate Caspase-7 to selectively kill cancer cells. Dr. Liang collaborated with the Genomics Research Center, Academia Sinica and two local hospitals using drug-resistant cancers cells and cancer cells that cause poor prognosis in cancer patients as subjects. The research results was published on-line by the Journal of Clinical Investigation on ... Read more

Tao-Hsin Chang, Shu-Jung Chang, Fu-Lien Hsieh, Tzu-Ping Ko, Cheng-Tse Lin, Meng-Ru Ho, Iren Wang, Shang-Te Danny Hsu, Rey-Ting Guo, Wen Chang, and Andrew H.-J. Wang
Research teams led by Dr. Andrew H.-J. Wang (IBC) and Dr. Wen Chang (IMB) have joined the effort to solve the crystal structure of a vaccinia envelope A27 protein and showed that the protein trimer is the structural unit critical for vaccinia virus egress as well as controlling viral fusion suppressor complex formation. The findings shed light on the viral fusion regulation mechanism of vaccinia virus, a member of poxvirus family that also contains ... Read more

J.-H. Liao, K. Ihara, C.-I. Kuo, K.-F. Huang, S. Wakatsuki, S.-H. Wu and C.-I. Chang
A research team led by Associate Research Fellow Dr. Chung-I Chang and Distinguished Research Fellow Dr. Shih-Hsiung Wu from the Institute of Biological Chemistry, Academia Sinica has resolved the structure of a LonC protease from Meiothermus taiwanensis, a domestic bacterium from hot springs in Wu-rai, Taiwan. The findings, which may shed light on new drugs design ... Read more

Tu Z, Lin YN, Lin CH
L-Fucose-containing glycoconjugates play an indispensible role in a myriad of physiological and pathological activities, such as inflammation, bacterial and viral infections, tumor metastasis and genetic disorders.
Fucosyltransferases (FucTs) and fucosidases, the main enzymes involved in the incorporation and cleavage of L-fucose residues, respectively, represent captivating targets for therapeutic treatment ... Read more

Chang YM, Chen CK, Ko TP, Chang-Chien MW, Wang AH
Staphylococci cause a wide range of diseases in human and animals such as skin infections, pneumonia, food poisoning and blood poisoning. They are notorious for their ability to develop resistance to antibiotics almost as soon as they are approved for clinical use and are the scourge of hospitals where they can cause death in patients admitted for other diseases. The multiple antibiotic resistance repressor (MarR) family proteins ... Read more


High-resolution structures of Neotermes koshunensis beta-glucosidase mutants provide insights into the catalytic mechanism and the synthesis of glucoconjugates.
Jeng WY, Wang NC, Lin CT, Chang WJ, Liu CI, Wang AH. Acta Crystallogr D Biol Crystallogr. DOI: 10.1107/S0907444912013224

In Vivo tagging and characterization of s-glutathionylated proteins by a chemoenzymatic method.
Chiang BY, Chou CC, Hsieh FT, Gao S, Lin JC, Lin SH, Chen TC, Khoo KH, Lin CH. Angew Chem Int Ed Engl. DOI: 10.1002/anie.201200321

miR-103/107 promote metastasis of colorectal cancer by targeting the metastasis suppressors DAPK and KLF4.
Chen HY, Lin YM, Chung HC, Lang YD, Lin CJ, Huang J, Wang WC, Lin FM, Chen Z, Huang HD, Shyy JY, Liang JT*, Chen RH* Cancer Res. DOI: 10.1158/0008-5472.CAN-12-0667


The calcium-chelating capability of tetrahydrofuranic moieties modulates the cytotoxicity of annonaceous acetogenins.
Liaw CC, Liao WY, Chen CS, Jao SC, Wu YC, Shen CN, Wu SH. Angew Chem Int Ed Engl. DOI: 10.1002/anie.201100717

Atg1-mediated myosin II activation regulates autophagosome formation during starvation-induced autophagy.
Tang HW, Wang YB, Wang SL, Wu MH, Lin SY, Chen GC. EMBO J. DOI: 10.1038/emboj.2010.338

A Cullin3-KLHL20 Ubiquitin ligase-dependent pathway targets PML to potentiate HIF-1 signaling and prostate cancer progression.
Yuan WC, Lee YR, Huang SF, Lin YM, Chen TY, Chung HC, Tsai CH, Chen HY, Chiang CT, Lai CK, Lu LT, Chen CH, Gu DL, Pu YS, Jou YS, Lu KP, Hsiao PW, Shih HM, Chen RH. Cancer Cell. DOI: 10.1016/j.ccr.2011.07.008


Structural basis of alpha-fucosidase inhibition by iminocyclitols with K(i) values in the micro- to picomolar range.
Wu HJ, Ho CW, Ko TP, Popat SD, Lin CH, Wang AH. Angew Chem Int Ed Engl. DOI: 10.1002/anie.200905597

Mechanism of action and inhibition of dehydrosqualene synthase.
Lin FY, Liu CI, Liu YL, Zhang Y, Wang K, Jeng WY, Ko TP, Cao R, Wang AH, Oldfield E. Proc Natl Acad Sci U S A. DOI: 10.1073/pnas.1010907107

Structure of a heterotetrameric geranyl pyrophosphate synthase from mint (Mentha piperita) reveals intersubunit regulation.
Chang TH, Hsieh FL, Ko TP, Teng KH, Liang PH, Wang AH. Plant Cell. DOI: 10.1105/tpc.109.071738

The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquitination to control interferon responses.
Lee YR, Yuan WC, Ho HC, Chen CH, Shih HM, Chen RH. EMBO J. DOI: 10.1038/emboj.2010.62


Role for alpha-L-fucosidase in the control of Helicobacter pylori-infected gastric cancer cells.
Liu TW, Ho CW, Huang HH, Chang SM, Popat SD, Wang YT, Wu MS, Chen YJ, Lin CH. Proc Natl Acad Sci U S A. DOI: 10.1073/pnas.0903286106

Phosphoproteomics of Klebsiella pneumoniae NTUH-K2044 reveals a tight link between tyrosine phosphorylation and virulence.
Lin MH, Hsu TL, Lin SY, Pan YJ, Jan JT, Wang JT, Khoo KH, Wu SH. Mol Cell Proteomics. DOI: 10.1074/mcp.M900276-MCP200

Glycomics and proteomics analyses of mouse uterine luminal fluid revealed a predominance of Lewis Y and X epitopes on specific protein carriers.
Kuo CW, Chen CM, Lee YC, Chu ST, Khoo KH. Mol Cell Proteomics. DOI: 10.1074/mcp.M800320-MCP200

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