中央研究院 生物化學研究所

研究領域與專長

Our laboratory has been focusing on (i) mechanistic and structural studies of prenyltransferases catalyzing chain elongation, such as undecaprenyl diphosphate synthase, octaprenyl diphosphate synthase, and geranylgeranyl diphosphate synthase; (ii) antivirus and anti-cancer drug discovery targeting 3C protease from Enterovirus 71, 3C-like proteases from SARS-CoV and MERS-CoV, neuraminidase from avian flu virus, and protein-protein interactions; (iii) multi-functional cellulose/hemicellulose degrading enzymes for biofuel production.

學經歷

• 1989 – 1994   博士, 化學暨生化系, 美國馬里蘭大學
• 1982 – 1986   學士, 化學系, 臺灣大學。

• 2009 – 迄今   理事, 臺灣生物化學及分子生物學學會
• 2007 – 迄今   合聘教授, 臺大生命科學院生化所
• 2007 – 迄今   編輯委員, Bioorganic Chemistry (Elsevier) and JCCS
• 2006 – 迄今   研究員, 中研院生化所
• 2017 – 2019   代理副所長, 中央研究院生物化學研究所
• 2017 – 2017   副所長, 中央研究院生物化學研究所
• 2010 – 2015   理事, 亞太蛋白質學會
• 2007 – 2016   理事, 中華民國生物物理學會
• 2006 – 2011   副所長, 中研院生化所
• 2005 – 2008   主持人, 重組蛋白生產核心設施
• 2004 – 2011   Chem Biology & Mol Biophys 召集人, 中研院國際研究生學程
• 2002 – 2006   副研究員, 中研院生化所
• 1999 – 2002   助研究員, 中研院生化所
• 1996 – 1999   研究員, 史克美占藥廠巨分子科學及蛋白質化學系
• 1995 – 1996   助理研究員, 美國耶魯大學醫學院藥學系
• 1994 – 1995   博士後研究員, 美國耶魯大學醫學院藥學系

主要著作

Identification and evaluation of potent Middle East respiratory syndrome coronavirus (MERS-CoV) 3CLpro inhibitors. 
Kumar V, Shin JS, Shie JJ, Ku KB, Kim C, Go YY, Huang KF, Kim M, Liang PH 
Antiviral research (2017)

Fluorescent farnesyl diphosphate analogue: A probe to validate trans-prenyltransferase inhibitors. 
Teng KH, Hsu ET, Chang YH, Lin SW, Liang PH 
BIOCHEMISTRY (2016)

Biochemical characterization and structural analysis of a bifunctional cellulase/xylanase from Clostridium thermocellum. 
Yuan SF, Wu TH, Lee HL, Hsieh HY, Lin WL, Yang B, Chang CK, Li Q, Gao J, Huang CH, Ho MC, Guo RT, Liang PH 
The Journal of biological chemistry (2015)

Identification, synthesis and evaluation of new neuraminidase inhibitors. 
Kumar V, Chang CK, Tan KP, Jung YS, Chen SH, Cheng, YS, Liang PH 
Organic Letters (2014)

Control activity of yeast geranylgeranyl diphosphate synthase from dimer interface through H-bonds and hydrophobic interaction. 
Chang CK, Teng KH, Lin SW, Chang TH, Liang PH 
Biochemistry (2013)

Targeting the XIAP/caspase-7 complex selectively kills caspase-3 deficient malignancies. 
Lin, Y. F. Lai, T. C., Chang, C. K., Chen, C.L., Huang, M.S., Yang, C.J., Liu, H. G., Dong, J. J., Chou, Y.A., Teng, K. H., Chen, S. H., Tian, W. T., Jan, Y. H., Hsiao, M., and Liang, P. H. 
J. Clinical Investigation (2013)

Targeting β-tubulin:CCT-β complexes incurs Hsp90- and VCP-related protein degradation and induces ER stress-associated apoptosis by triggering capacitative Ca²⁺ entry, mitochondrial perturbation and caspase overactivation. 
Lin YF, Lee YF, Liang PH 
Cell Death & Disease (2012)

Construction and characterization of different fusion proteins between cellulases and β-glucosidase to improve glucose production and thermostability. 
Lee HL, Chang CK, Teng KH, Liang PH 
BIORESOURCE TECHNOLOGY (2011)

Combined experimental and theoretical study of long-range interactions modulating dimerization and activity of yeast geranylgeranyl diphosphate synthase. 
Chia-Hsiang Lo, Ying-Hsuan Chang, Jon D. Wright, Shih-Hsun Chen, Daphne Kan, Carmay Lim, and Po-Huang Liang 
Journal of the American Chemical Society (2009)

Intracellular beta-tubulin/Chaperonin containing TCP1-beta complex serves as a novel chemotherapeutic target against drug-resistant tumors. 
Yuan-Feng Lin, Wen-Ping Tsai, Hon-Ge Liu, and Po-Huang Liang 
Cancer Research (2009)

著作列表

1. Kuo CJ*, (Liang PH)*  (2022-05)  FEBS letters  596(9), 1214-1224  "SARS-CoV-2 3CL(pro) displays faster self-maturation in vitro than SARS-CoV 3CL(pro) due to faster C-terminal cleavage."
   
2. Yu PC, Huang CH, Kuo CJ, (Liang PH), Wang LH, Pan MY, Chang SY, Chao TL, Ieong SM, Fang JT, Huang HC, Juan HF  (2022-01)  Pharmaceutics  14(1), 176  "Drug Repurposing for the Identification of Compounds with Anti-SARS-CoV-2 Capability via Multiple Targets."
   
3. Lee JY, Kuo CJ, Soo Shin J, Jung E, (Liang PH)*, Jung YS*  (2021-06)  Bioorganic & Medicinal Chemistry Letters  42, 128067  "Identification of non-covalent 3C-like protease inhibitors against severe acute respiratory syndrome coronavirus-2 via virtual screening of a Korean compound library"
   
4. Lo HS, Hui KPY, Lai HM, He X, Khan KS, Kaur S, Huang J, Li Z, Chan AKN, Cheung HH, Ng KC, Ho JCW, Chen YW, Ma B, Cheung PM, Shin D, Wang K, Lee MH, Selisko B, Eydoux C, Guillemot JC, Canard B, Wu KP, (Liang PH), Dikic I, Zuo Z, Chan FKL, Hui DSC, Mok VCT, Wong KB, Mok CKP, Ko H, Aik WS, Chan MCW, Ng WL  (2021-05)  ACS central science  7(5), 792-802  "Simeprevir Potently Suppresses SARS-CoV-2 Replication and Synergizes with Remdesivir."
   
5. Kuo CJ, Chao TL, Kao HC, Tsai YM, Liu YK, Wang LH, Hsieh MC, Chang SY*, (Liang PH)*  (2021-03)  Antimicrobial Agents and Chemotherapy  65(4), e02577-20  "Kinetic characterization and inhibitor screening for the proteases leading to identification of drugs against SARS-CoV-2."
   
6. Pathak N, Chen YT, Hsu YC, Hsu NY, Kuo CJ, Tsai HP, Kang JJ, Huang CH, Chang SY, Chang YH, (Liang PH), Yang JM  (2021-01)  ACS Nano  15(1), 857-872  "Uncovering Flexible Active Site Conformations of SARS-CoV-2 3CL Proteases through Protease Pharmacophore Clusters and COVID-19 Drug Repurposing."
   
7. Chang YX, Lin YF, Chen CL, Huang MS, Hsiao M, (Liang PH)*  (2020-12)  Cancers  12(12), 3865  "Chaperonin-Containing TCP-1 Promotes Cancer Chemoresistance and Metastasis through the AKT-GSK3β-β-Catenin and XIAP-Survivin Pathways."
   
8. Liu YJ, Chang YJ, Kuo YT, (Liang PH)  (2020-05)  Carcinogenesis  41(5), 699-710  "Targeting beta-tubulin/CCT-beta complex induces apoptosis and suppresses migration and invasion of highly metastatic lung adenocarcinoma."
   
9. Yao JY, Teng KH, Liu MC, Wang CS, (Liang PH)*  (2019-07)  Molecules  24(15), 2728  "Characterization of a Cis-Prenyltransferase from Lilium longiflorum Anther"
   
10. Chen CH, Yao JY, Yang B, Lee HL, Yuan SF, Hsieh HY, (Liang PH)  (2019-02)  Bioresource Technology Reports  5, 170-177  "Engineer multi-functional cellulase/xylanase/β-glucosidase with improved efficacy to degrade rice straw."
    
11. Hsieh MH, Huang PT, Liou HH, (Liang PH), Chen PM, Holt SA, Yu IF, James M, Shiau YS, Lee MT, Lin TL, Lou KL  (2018-07)  Langmuir  34(30), 9036-9046  "The Penetration Depth for Hanatoxin Partitioning into the Membrane Hydrocarbon Core Measured with Neutron Reflectivity."
    
12. Huang KH, Fang WL, Li AF, (Liang PH), Wu CW, Shyr YM, Yang MH  (2018-04)  International journal of surgery  52, 258-263  "Caspase-3, a key apoptotic protein, as a prognostic marker in gastric cancer after curative surgery."
    
13. Thirumalraj B, Dhenadhayalan N, Chen SM*, Liu YJ, Chen TW, (Liang PH), Lin KC*  (2018-04)  Sensors & Actuators B - Chemical  259, 339–346  "Highly sensitive fluorogenic sensing of L-Cysteine in live cells using gelatin-stabilized gold nanoparticles decorated graphene nanosheets."
    
14. (Liang PH), Lin WL, Hsieh HY, Lin TY, Chen CH, Tewary SK, Lee HL, Yuan SF, Yang B, Yao JY, Ho MC  (2018-03)  Biochimica et Biophysica Acta - General Subjects  1862(3), 513-521  "A flexible loop for mannan recognition and activity enhancement in a bifunctional glycoside hydrolase family 5."
    
15. Liu YJ, Kumar V, Lin YF, (Liang PH)  (2017-09)  Cell death & disease  8(9), e3052  "Disrupting CCT-beta : beta-tubulin selectively kills CCT-beta overexpressed cancer cells through MAPKs activation."
    
16. Kumar V, Shin JS, Shie JJ, Ku KB, Kim C, Go YY, Huang KF, Kim M, (Liang PH)  (2017-05)  Antiviral research  141, 101-106  "Identification and evaluation of potent Middle East respiratory syndrome coronavirus (MERS-CoV) 3CLPro inhibitors."
    
17. Teng KH, Hsu ET, Chang YH, Lin SW, (Liang PH)  (2016-08)  BIOCHEMISTRY  55(31), 4366-4374  "Fluorescent Farnesyl Diphosphate Analogue: A Probe To Validate trans-Prenyltransferase Inhibitors."
    
18. Kumar V, Tan KP, Wang YM, Lin SW, (Liang PH)  (2016-07)  Bioorganic & medicinal chemistry  24(13), 3035-3042  "Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C-like protease inhibitors."
    
19. Tsai LC, Amiraslanov I, Chen HR, Chen YW, Lee HL, (Liang PH), Liaw YC  (2015-10)  Acta Crystallographica Section F-Structural Biology Communications  71(Pt 10), 1264-1272  "Structures of exoglucanase from Clostridium cellulovorans: cellotetraose binding and cleavage."
    
20. Kuo CJ, (Liang PH)  (2015-04)  CHEMBIOENG REVIEWS  2(2), 118–132  "Characterization and Inhibition of the Main Protease of Severe Acute Respiratory Syndrome Coronavirus."
    
21. Yuan SF, Wu TH, Lee HL, Hsieh HY, Lin WL, Yang B, Chang CK, Li Q, Gao J, Huang CH, Ho MC, Guo RT, (Liang PH)  (2015-02)  The Journal of biological chemistry  290(9), 5739-5748  "Biochemical Characterization and Structural Analysis of a Bifunctional Cellulase/Xylanase from Clostridium thermocellum."
    
22. Han X, Chen CC, Kuo CJ, Huang CH, Zheng Y, Ko TP, Zhu Z, Feng X, Wang K, Oldfield E, Wang AH, (Liang PH), Guo RT, Ma Y  (2015-01)  Proteins  83(1), 37-45  "Crystal structures of ligand-bound octaprenyl pyrophosphate synthase from Escherichia coli reveal the catalytic and chain-length determining mechanisms."
    
23. Kumar V, Chang CK, Tan KP, Jung YS, Chen SH, Cheng YS, (Liang PH)  (2014-10)  Organic letters  16(19), 5060-5063  "Identification, Synthesis, and Evaluation of New Neuraminidase Inhibitors."
    
24. Chan HC, Feng X, Ko TP, Huang CH, Hu Y, Zheng Y, Bogue S, Nakano C, Hoshino T, Zhang L, Lv P, Liu W, Crick DC, (Liang PH), Wang AH, Oldfield E, Guo RT  (2014-02)  Journal of the American Chemical Society  136(7), 2892-2896  "Structure and inhibition of tuberculosinol synthase and decaprenyl diphosphate synthase from Mycobacterium tuberculosis."
    
25. Al-Mudaris ZA, Majid AS, Ji D, Al-Mudarris BA, Chen SH, (Liang PH), Osman H, Jamal Din SK, Abdul Majid AM  (2013-11)  PloS one  8(11), e80983  "Conjugation of benzylvanillin and benzimidazole structure improves DNA binding with enhanced antileukemic properties."
    
26. Kumar V, Jung YS, (Liang PH)  (2013-10)  Expert opinion on therapeutic patents  23(10), 1337-1348  "Anti-SARS coronavirus agents: a patent review (2008 - present)."
    
27. Chen SH, Lin SW, Lin SR, (Liang PH), Yang JM  (2013-09)  Journal of chemical information and modeling  53(9), 2299-2311  "Moiety-Linkage Map Reveals Selective Nonbisphosphonate Inhibitors of Human Geranylgeranyl Diphosphate Synthase."
    
28. Lin YF, Lai TC, Chang CK, Chen CL, Huang MS, Yang CJ, Liu HG, Dong JJ, Chou YA, Teng KH, Chen SH, Tian WT, Jan YH, Hsiao M, (Liang PH)  (2013-09)  The Journal of clinical investigation  123(9), 3861-3875  "Targeting the XIAP/caspase-7 complex selectively kills caspase-3-deficient malignancies."
    
29. Hwang CC, Chang YH, Lee HJ, Wang TP, Su YM, Chen HW, (Liang PH)  (2013-05)  PloS one  8(5), e63594  "The catalytic roles of P185 and T188 and substrate-binding loop flexibility in 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni."
    
30. Chang CK, Teng KH, Lin SW, Chang TH, (Liang PH)  (2013-04)  Biochemistry  52(16), 2783-2792  "Control activity of yeast geranylgeranyl diphosphate synthase from dimer interface through H-bonds and hydrophobic interaction."
    
31. Lee HL, Chang CK, Jeng WY, Wang AH, (Liang PH)  (2012-11)  Protein engineering design & selection  25(11), 733-740  "Mutations in the substrate entrance region of beta-glucosidase from Trichoderma reesei improve enzyme activity and thermostability."
    
32. Lin YF, Lee YF, (Liang PH)  (2012-11)  Cell Death & Disease  3, e434  "Targeting β-tubulin:CCT-β complexes incurs Hsp90 and VCP-related protein degradation and induces ER stress-associated apoptosis by triggering capacitative Ca2+ entry, mitochondrial perturbation and caspase overactivation. "
    
33. Kuo-Hsun Teng, (Po-Huang Liang)*  (2012-08)  BIOORGANIC CHEMISTRY  43, 51-57  "Structures, mechanisms and inhibitors of undecaprenyl diphosphate synthase: A cis-prenyltransferase for bacterial peptidoglycan biosynthesis "
    
34. Ren F, Ko TP, Feng X, Huang CH, Chan HC, Hu Y, Wang K, Ma Y, (Liang PH), Wang AH, Oldfield E, Guo RT.  (2012-04)  ANGEWANDTE CHEMIE-INTERNATIONAL EDITION  51(17), 4157-4160  "Insights into the Mechanism of the Antibiotic-Synthesizing Enzyme MoeO5 from Crystal Structures of Different Complexes."
    
35. Chang KM, Chen SH, Kuo CJ, Chang CK, Guo RT, Yang JM, (Liang PH).  (2012-04)  BIOCHEMISTRY  51(6), 3412-3419  "Roles of Amino Acids in the Escherichia coli Octaprenyl Diphosphate Synthase Active Site Probed by Structure-Guided Site-Directed Mutagenesis."
    
36. Kesavulu MM, Tsai JY, Lee HL, (Liang PH), Hsiao CD.  (2012-03)  ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY  68, 310-320  "Structure of the catalytic domain of the Clostridium thermocellum cellulase CelT."
    
37. Teng KH, (Liang PH)  (2012)  Molecular membrane biology  29(7), 267-273  "Undecaprenyl diphosphate synthase, a cis-prenyltransferase synthesizing lipid carrier for bacterial cell wall biosynthesis."
    
38. Teng KH, Chen AP, Kuo CJ, Li YC, Liu HG, Chen CT, (Liang PH)  (2011-10)  Analytical biochemistry  417(1), 136-141  "Fluorescent substrate analog for monitoring chain elongation by undecaprenyl pyrophosphate synthase in real time."
    
39. R. Ramajayam, Kian-Pin Tan, (Po-Huang Liang)*  (2011-10)  BIOCHEMICAL SOCIETY TRANSACTIONS  39(5), 1371-1375  "Recent development of 3C and 3CL protease inhibitors for anti-coronavirus and anti-picornavirus drug discovery"
    
40. Lee HL, Chang CK, Teng KH, (Liang PH)  (2011-02)  BIORESOURCE TECHNOLOGY  102(4), 3973-3976  "Construction and characterization of different fusion proteins between cellulases and β-glucosidase to improve glucose production and thermostability."
    
41. Lei GS, Syu WJ, (Liang PH), Chak KF, Hu WS, Hu ST  (2011-02)  BMC MICROBIOLOGY  11(1), 33  "Repression of btuB gene transcription in Escherichia coli by the GadX protein"
    
42. Jeng WY, Wang NC, Lin MH, Lin CT, Liaw YC, Chang WJ, Liu CI, (Liang PH), Wang AH  (2011-01)  Journal of structural biology  173(1), 46-56  "Structural and functional analysis of three beta-glucosidases from bacterium Clostridium cellulovorans, fungus Trichoderma reesei and termite Neotermes koshunensis."
    
43. (Po-Huang Liang)  (2011)  CHEMISTRY AND PHYSICS OF LIPIDS  164(S1), S12-S14  "Kinetic, mechanistic, structural and inhibitory aspects of the cis-prenyltransferase catalyzed lipid chain elongation."
    
44. Wen, C. C., Shyur, L. F., Jan, J. T., (Po-Huang Liang), Kuo, C. J., Arulselvan, P., Wu, J. B., Kuo, S. C. And Yang, N. S.  (2011)  Journal of Traditional and Complementary Medicine  1, 41-50  "Traditional Chinese medicine herbal extracts of Cibotium barometz, Gentiana scabra, Dioscorea batatas, Cassia tora, and Taxillus chinensis inhibit SARS-CoV replication"
    
45. Ramajayam R, Tan KP, Liu HG, (Liang PH)  (2010-11)  BIOORGANIC & MEDICINAL CHEMISTRY  18(22), 7849-7854  "Synthesis and evaluation of pyrazolone compounds as SARS-coronavirus 3C-like protease nhibitors"
    
46. Lu YP, Liu HG, Teng KH, (Liang PH)  (2010-10)  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS  400(4), 758-762  "Mechanism of cis-prenyltransferase reaction probed by substrate analogues"
    
47. Ramajayam R, Tan KP, Liu HG, (Liang PH)  (2010-06)  Bioorganic & medicinal chemistry letters  20(12), 3569-3572  "Synthesis, docking studies, and evaluation of pyrimidines as inhibitors of SARS-CoV 3CL protease"
    
48. Chang TH, Hsieh FL, Ko TP, Teng KH, (Liang PH), Wang AH  (2010-02)  PLANT CELL  22(2), 454-467  "Structure of a Heterotetrameric Geranyl Pyrophosphate Synthase from Mint (Mentha piperita) Reveals Intersubunit Regulation."
    
49. Chan WC, (Liang PH), Shih YP, Yang UC, Lin WC, Hsu CN.*  (2010-01)  BMC Bioinformatics  11(Suppl 1), S21  "Learning to predict expression efficacy of vectors in recombinant protein production"
    
50. Wang HM, (Liang PH)  (2010-01)  Expert opinion on therapeutic patents  20(1), 59-71  "Picornaviral 3C protease inhibitors and the dual 3C protease/coronaviral 3C-like protease inhibitors."
    
51. Ahn TY, Kuo CJ, Liu HG, Ha DC, (Liang PH), Jung YS  (2010-01)  BULLETIN OF THE KOREAN CHEMICAL SOCIETY  31(01), 87-91  "Synthesis and evaluation of benzoquinolinone derivatives as SARS-CoV 3CL protease inhibitors"
    
52. Kuo CJ, Shih YP, Kan D, Liang PH  (2009-12)  BioTechniques  47(6), 1029–1032  "Engineering a novel endopeptidase based on SARS 3CLpro"
    
53. Hui-Min Wang, Yan-Ping Shih, Su-Ming Hu, Wen-Tsung Lo, Hui-Min Lin, Shih-Shiu Ding, Hsin-Chi Liao, and (Po-Huang Liang)*  (2009-11)  Biotechnology Progress  25(6), 1582-1586  "Parallel gene cloning and protein production in multiple expression systems"
    
54. Chia-Hsiang Lo, Ying-Hsuan Chang, Jon D. Wright, Shih-Hsun Chen, Daphne Kan, Carmay Lim, and (Po-Huang Liang)*  (2009)  Journal of the American Chemical Society  131, 4051-4062  "Combined experimental and theoretical study of long-range interactions modulating dimerization and activity of yeast geranylgeranyl diphosphate synthase"
    
55. Lu YP, Liu HG, Liang PH  (2009)  Biochemical and biophysical research communications  379(2), 351-355  "Different reaction mechanisms for cis- and trans-prenyltransferases."
    
56. Kuo CJ, Liu HG, Lo YK, Seong CM, Lee KI, Jung YS, Liang PH  (2009)  FEBS letters  583(3), 549-555  "Individual and common inhibitors of coronavirus and picornavirus main proteases."
    
57. Yuan-Feng Lin, Wen-Ping Tsai, Hon-Ge Liu, and (Po-Huang Liang)*  (2009)  Cancer Research  69, 6879-6888  "Intracellular beta-tubulin/Chaperonin containing TCP1-beta complex serves as a novel chemotherapeutic target against drug-resistant tumors"
    
58. (Po-Huang Liang)*  (2009)  Biochemistry  48, 6562-6570  "Reaction kinetics, catalytic mechanisms, conformational changes, and inhibitor design for prenyltransferases"
    
59. Lee CC, Kuo CJ, Ko TP, Hsu MF, Tsui YC, Chang SC, Yang S, Chen SJ, Chen HC, Hsu MC, Shih SR, (Liang PH), Wang AH  (2009)  The Journal of biological chemistry  284(12), 7646-7655  "Structural basis of inhibition specificities of 3C and 3C-like proteases by zinc-coordinating and peptidomimetic compounds."
    
60. Lee JC, Shih SR, Chang TY, Tseng HY, Shih YF, Yen KJ, Chen WC, Shie JJ, Fang JM, Liang PH, Chao YS, Hsu JT.  (2008)  Anal Biochemistry  375, 115-123  "A mammalian cell-based reverse two-hybrid system for functional analysis of 3C viral protease of human enterovirus 71"
    
61. C. J. Kuo, J. J. Shie, J. M. Fang, G. R. Yen, J. T. Hsu, H. G. Liu, S. N. Tseng, S. C. Chang, C. Y. Lee, S. R. Shih and P. H. Liang  (2008)  BIOORGANIC & MEDICINAL CHEMISTRY  16, 7388-7398  "Design, synthesis, and evaluation of 3C protease inhibitors as anti-enterovirus 71 agents"
    
62. Y. M. Shao, W. B. Yang, T. H. Kuo, K. C. Tsai, C. H. Lin, A. S. Yang, P. H. Liang and C. H. Wong  (2008)  BIOORGANIC & MEDICINAL CHEMISTRY  16, 4652-4660  "Design, Synthesis, and evaluation of trifluoromethyl ketones as inhibitors of SARS-CoV 3CL protease"
    
63. K. M. Chen et al.  (2008)  J. Med. Chem  51, 5594-5607  "Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation"
    
64. C. J. Kuo, R. T. Guo, I. L. Lu, H. G. Liu, S. Y. Wu, T. P. Ko, A. H. J. Wang and P. H. Liang*  (2008)  J Biomed Biotechnol  841312  "Structure-based inhibitors exhibited differential activities against H. pylori and E. coli undecaprenyl pyrophosphate synthases"
    
65. R. T. Guo, R. Cao, P. H. Liang, T. P. Ko, T. H. Chang, M. P. Hudock, W. Y. Jeng, C. K. Chen, Y. Zhang, Y. Song, C. J. Kuo, F. Yin, E. Oldfield and A. H. Wang  (2007)  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA  104, 10022-10027  "Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases"
    
66. P. H. Liang  (2007)  Drugs of the Future  32, 29-29  "Drug discovery for SARS and other human coronaviruses targeting 3C proteases"
    
67. C. W. Yang, Y. N. Yang, P. H. Liang, C. M. Chen, W. L. Chen, H. Y. Chang, Y. S. Chao and S. J. Lee  (2007)  Antimicrob Agents Chemother  51(11), 3924-3931  "Novel small-molecule inhibitors of transmissible gastroenteritis virus"
    
68. H. M. Wang and P. H. Liang  (2007)  Expert Opinion on Therapeutic Patents  17, 533-546  "Pharmacophores and biological activities of severe respiratory syndrome viral protease inhibitors"
    
69. C. C. Wen, Y. H. Kuo, J. T. Jan, P. H. Liang, S. Y. Wang, H. G. Liu, C. K. Lee, S. T. Chang, C. J. Kuo, S. S. Lee, C. C. Hou, P. W. Hsiao, S. C. Chien, L. F. Shyur and N. S. Yang  (2007)  J Med Chem  50, 4087-4095  "Specific Plant Terpenoids and Lignoids Possess Potent Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus"
    
70. C. C. Lee, C. J. Kuo, M. F. Hsu, P. H. Liang, J. M. Feng, J. J. Shie and A. H. J. Wang  (2007)  FEBS Lett  581, 5454-5458  "Structural basis of mercury- and zinc-conjugated complexes as SARS-CoV 3C-like protease inhibitors"
    
71. Y. M. Shao, W. B. Yang, H. P. Peng, M. F. Hsu, K. C. Tsai, T. H. Kuo, A. H. Wang, P. H. Liang, C. H. Lin, A. S. Yang and C. H. Wong  (2007)  Chembiochem  8, 1654-1657  "Structure-Based Design and Synthesis of Highly Potent SARS-CoV 3CL Protease Inhibitors"
    
72. Y. Y. Lee, H. T. Hu, P. H. Liang and C. F. Chak  (2006)  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS  345, 1579-1585  "An E. coli lon mutant conferring partial resistance to colicin may reveal a novel role in regulating proteins involved in the translocation of colicin"
    
73. P. H. Liang  (2006)  Current Topics in Medicinal Chemistry  6, 361-376  "Characterization and inhibition of SARS-coronavirus main protease"
    
74. D. H. Chang, R. T. Guo, T. P. Ko, A. H.-J. Wang and P. H. Liang  (2006)  J Biol Chem  281, 14991-15000  "Crystal structure of type-III geranylgeranyl pyrophosphate synthase from Saccharomyces cerevisiae and the mechanism of product chain length determination"
    
75. K. C. Tsai, S. Y. Chen, P. H. Liang, I. L. Luo, N. Mahindroo, S. P. Hsieh, Y. S. Chao, W. Lien, T. H. Lin and S. Y. Wu  (2006)  J Med Chem  49, 3485-3495  "Discovery of a novel family of SARS-CoV protease inhibitors by virtual screening and 3D-QSAR studies"
    
76. T. H. Kuo, S. C. Chuang, S. Y. Chang and P. H. Liang  (2006)  Biochem J  393, 757-766  "Ligand specificities and structural requirements of two Tachypleus plasma lectins for bacterial trapping"
    
77. C. Y. Wu, K. Y. King, C. J. Kuo, Y. T. Wu, M. Y. Ho, C. L. Liao, J. M. Fang, P. H. Liang and C. H. Wong  (2006)  Chem Biol  13, 261-268  "Stable benzotriazole esters as mechanism-based inhibitors of the severe acute respiratory syndrome 3CL protease"
    
78. I. L. Lu, N. Mahindroo, P. H. Liang, C. J. Kuo, H. P. Hsieh, Y. S. Chao and S. Y. Wu  (2006)  J Med Chem  49, 5154-5161  "Structure-Based Drug Design and Structural Biology Study of Novel Nonpeptide Inhibitors of SARS-CoV Main Protease"
    
79. Y. H. Pan, C. C. Liao, C. C. Kuo, K. J. Duan, P. H. Liang, H. S. Yuan, S. T. Hu and K. F Chak  (2006)  J Biol Chem  281, 13083-13091  "The critical roles of polyamines in regulating ColE7 production and restricting ColE7 uptake of the colicin producing Escherichia coli"
    
80. R. T. Guo, T. P. Ko, A. P. C. Chen, C. J. Kuo, A. H. J. Wang and P. H. Liang  (2005)  J Biol Chem  280, 20762-20774  "Crystal structures of undecaprenyl pyrophosphate synthase in complex with magnesium, isopentenyl pyrophosphate and farnesyl thiopyrophosphate: Roles of the metal ion and conserved residues in catalysis"
    
81. J. J. Shie, J. M., Fang, C. J. Kuo, T. H. Kuo, P. H. Liang, H. J. Huang, W. B. Yang, C. H. Lin, J. L. Chen, Y. T. Wu and C. H. Wong  (2005)  J Med Chem  48, 4469-4473  "Discovery of potent anilide inhibitors against the severe acute respiratory syndrome 3CL protease"
    
82. Han-Yu Sun, Tzu-Ping Ko, Chih-Jung Kuo, Rey-Ting Guo, Chia-Cheng Chou, Po-Huang Liang and Andrew H.-J. Wang*  (2005)  J Bacteriol  187(23), 8137-8148  "Homodimeric Hexaprenyl Pyrophosphate Synthase from the Thermoacidophilic Crenarchaeon Sulfolobus solfataricus Displays Asymmetric Subunit Structures"
    
83. Chia-Nan Chen, Coney P. C. Lin, Kuo-Kuei Huang, Wei-Cheng Chen, Hsin-Pang Hsieh, Po-Huang Liang and John T.-A. Hsu*  (2005)  Evid Based Complement Alternat Med  2(2), 209-215  "Inhibition of SARS-CoV 3C-like Protease Activity by Theaflavin-3,3′-digallate (TF3)"
    
84. J. J. Shie, J. M. Fang, T. H. Kuo, C. J. Kuo, P. H. Liang, H. J. Huang, Y. T. Wu, J. T. Jan, Y. S. Cheng,and C. H. Wong  (2005)  BIOORGANIC & MEDICINAL CHEMISTRY  13, 5240-5252  "Inhibition of the severe acute respiratory syndrome 3CL protease by peptidomimetic alpha,beta-unsaturated esters."
    
85. M. F. Hsu, C. J. Kuo, K. T. Chang, H. C. Chang, C. C., Chou, T. P. Ko, H. L. Shr, G. G. Chang, A, H.-J. Wang and P. H. Liang  (2005)  J Biol Chem  280, 31257-31266  "Mechanism of the maturation process of SARS-CoV 3CL protease"
    
86. A. P. Chen, S. Y. Chang, Y. C. Lin, Y. S. Sun, C. T. Chen, A. H. Wang and P. H. Liang  (2005)  Biochem J  386, 169-176  "Substrate and product specificities of cis-type undecaprenyl pyrophosphate synthase"
    
87. R. T. Guo, C. J. Kuo, T. P. Ko, C. C. Chou, P. H. Liang and A. H. Wang  (2004)  Biochemistry  43, 7678-7686  "A molecular ruler for chain elongation catalyzed by octaprenyl pyrophosphate synthase and its structure-based engineering to produce unprecedented long chain trans-prenyl products"
    
88. C. J. Kuo, Y. H. Chi, J. T.A. Hsu and P. H. Liang  (2004)  Biochem Biophys Res Commun  318, 862-867  "Characterization of SARS main protease and inhibitor assay using a fluorogenic substrate"
    
89. R. T. Guo, C. J. Kuo, C. C. Chou, T. P. Ko, H. L. Shr, P. H. Liang and A. H. Wang  (2004)  J Biol Chem  279, 4903-4912  "Crystal structure of octaprenyl pyrophosphate synthase from hyperthermophilic Thermotoga maritima and mechanism of product chain length determination"
    
90. K. C. Hsia, K. F. Chak, P. H. Liang, Y. S. Cheng, W. Y. Ku and H. S. Yuan  (2004)  Structure (Camb)  12, 205-214  "DNA binding and degradation by the HNH protein ColE7"
    
91. J. T. Hsu, C. J. Kuo, H. P. Hsieh, Y. C. Wang, K. K. Huang, C. P. Lin, P. F. Huang, X. Chen and P. H. Liang  (2004)  FEBS Lett  574, 116-120  "Evaluation of metal-conjugated compounds as inhibitors of 3CL protease of SARS-CoV"
    
92. T. L. Chung, H. H. Hsiao, Y. Y. Yeh, H. L. Shia, Y. L. Chen, P. H. Liang, A. H. Wang, K. H. Khoo and S. L. Li  (2004)  J Biol Chem  279, 39653-39662  "In vitro modification of human centromere protein CENP-C fragments by small ubiquitin-like modifier (SUMO) protein: definitive identification of the modification sites by tandem mass spectrometry analysis of the isopeptides"
    
93. Y. H. Lin, C. C. Liao, P. H. Liang, H. S. Yuan and K. F. Chak  (2004)  Biochem Biophys Res Commun  318, 81-87  "Involvement of colicin in the limited protection of the colicin producing cells against bacteriophage"
    
94. C. H. Chien, L. H. Huang, C. Y. Chou, Y. S. Chen, Y. S. Han, G. G. Chang, P. H. Liang and X. Chen  (2004)  J Biol Chem  279, 52338-52345  "One site mutation disrupts dimer formation in human DPP-IV proteins"
    
95. Y. S. Chen, C. H. Chien, C. M. Goparaju, J. T. Hsu, P. H. Liang and X. Chen  (2004)  Protein Expr Purif  35, 142-146  "Purification and characterization of human prolyl dipeptidase DPP8 in Sf9 insect cells"
    
96. C. Y. Wu, J. T. Jan, S. H. Ma, C. J. Kuo, H. F. Juan, Y. S. Cheng, H. H. Hsu, H. C. Huang, D. Wu, A. Brik, F. S. Liang, R. S. Liu, J. M. Fang, S. T. Chen, P. H. Liang and C. H. Wong  (2004)  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA  101, 10012-10017  "Small molecules targeting severe acute respiratory syndrome human coronavirus"
    
97. S. Y. Chang, T. P. Ko, A. P. Chen, A. H. Wang and P. H. Liang  (2004)  Protein Sci  13, 971-978  "Substrate binding mode and reaction mechanism of undecaprenyl pyrophosphate synthase deduced from crystallographic studies"
    
98. S. Y. Chang, T. P. Ko, P. H. Liang and A. H. Wang  (2003)  J Biol Chem  278, 29298-29307  "Catalytic mechanism revealed by the crystal structure of undecaprenyl pyrophosphate synthase in complex with sulfate, magnesium, and triton"
    
99. S. Y. Chang, Y. K. Chen, A. H. Wang and P. H. Liang  (2003)  Biochemistry  42, 14452-14459  "Identification of the active conformation and the importance of length of the flexible loop 72-83 in regulating the conformational change of undecaprenyl pyrophosphate synthase"
    
100. R. T. Guo, T. P. Ko, C. C. Chou, H. L. Shr, H. M. Chu, Y. H. Tsai, P. H. Liang and A. H. Wang  (2003)  ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY  59, 2265-2268  "Preliminary X-ray diffraction analysis of octaprenyl pyrophosphate synthase crystals from Thermotoga maritima and Escherichia coli"
     
101. C. E. Atreya, E. F. Johnson, J. Williamson, S. Y. Chang, P. H. Liang and K. S. Anderson  (2003)  J Biol Chem  278, 28901-28911  "Probing electrostatic channeling in protozoal bifunctional thymidylate synthase-dihydrofolate reductase using site-directed mutagenesis"
     
102. S. M. Hu, P. H. Liang, C. D. Hsiao and C. Wang  (2002)  Arch Biochem Biophys  407, 135-141  "Characterization of the L399P and R447G mutants of hsc70: the decrease in refolding activity is correlated with an increase in the rate of substrate dissociation"
     
103. J. J. Pan, T. H. Kuo, Y. K. Chen, L. W. Yang and P. H. Liang  (2002)  BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY  1594, 64-73  "Insight into the activation mechanism of Escherichia coli octaprenyl pyrophosphate synthase derived from pre-steady-state kinetic analysis"
     
104. Y. H. Chen, A. P. Chen, C. T. Chen, A. H. Wang and P. H. Liang  (2002)  J Biol Chem  277, 7369-7376  "Probing the conformational change of Escherichia coli undecaprenyl pyrophosphate synthase during catalysis using an inhibitor and tryptophan mutants"
     
105. T. H. Kuo, P. H. Liang  (2002)  Biochimica et Biophysica Acta-Proteins and Proteomics  1599, 125-133  "Reaction kinetic pathway of the recombinant octaprenyl pyrophosphate synthase from Thermotoga maritima: how is it different from that of the mesophilic enzyme"
     
106. P. H. Liang, T. P. Ko and A. H. Wang  (2002)  Eur J Biochem  269, 3339-3354  "Structure, mechanism and function of prenyltransferases"
     
107. A. P. Chen, Y. H. Chen, H. P. Liu, Y. C. Li, C. T. Chen and P. H. Liang  (2002)  J Am Chem Soc  124, 15217-15224  "Synthesis and application of a fluorescent substrate analogue to study ligand interactions for undecaprenyl pyrophosphate synthase"
     
108. W. Y. Ku, Y. W. Liu, Y. C. Hsu, C. C. Liao, P. H. Liang, H. S. Yuan and K. F. Chak  (2002)  Nucleic Acids Res  30, 1670-1678  "The zinc ion in the HNH motif of the endonuclease domain of colicin E7 is not required for DNA binding but is essential for DNA hydrolysis"
     
109. T. P. Ko, Y. K. Chen, H. Robinson, P. C. Tsai, Y. G. Gao, A. P. Chen, A. H. Wang and P. H. Liang  (2001)  J Biol Chem  276, 47474-47482  "Mechanism of product chain length determination and the role of a flexible loop in Escherichia coli undecaprenyl-pyrophosphate synthase catalysis"
     
110. C. C. Liao, K. C. Hsiao, Y. W. Liu, P. H. Leng, H. S. Yuen and K. F. Chak  (2001)  Biochem Biophys Res Commun  284, 556-562  "Processing of DNase domain during translocation of colicin E7 across the membrane of Escherichia coli"
     
111. S. Y. Chang, P. C. Tsai, C. S. Tseng and P. H. Liang  (2001)  Protein Expr Purif  23, 432-439  "Refolding and characterization of a yeast dehydrodolichyl diphosphate synthase overexpressed in Escherichia coli"
     
112. G. Yang, R. B. Kirkpatrick, T. Ho, G. F. Zhang, P. H. Liang, K. O. Johanson, D. J. Casper, M. L. Doyle, J. P. Marino Jr, S. K. Thompson, W. Chen, D. G. Tew and T. D. Meek  (2001)  Biochemistry  40, 10645-10654  "Steady-state kinetic characterization of substrates and metal-ion specificities of the full-length and N-terminally truncated recombinant human methionine aminopeptidases (type 2)"
     
113. J. J. Pan, L. W. Yang and P. H. Liang  (2000)  Biochemistry  39, 13856-13861  "Effect of site-directed mutagenesis of the conserved aspartate and glutamate on E. coli undecaprenyl pyrophosphate synthase catalysis"
     
114. D. Lee, S. A. Long, J. L. Adams, G. Chan, K. S. Vaidya, T. A. Francis, K. Kikly, J. D. Winkler, C. M. Sung, C. Debouck, S. Richardson, M. A. Levy, W. E. DeWolf, Jr., P. M. Keller, T. Tomaszek, M. S. Head, M. D. Ryan, R. C. Haltiwanger, P. H. Liang, C. A. Janson, P. J. McDevitt, K. Johanson, N. O. Concha, W. Chan, S. S. Abdel-Meguid, A. M. Badger, M. W. Lark, D. P. Nadeau, L. J. Suva, M. Gowen and M. E. Nuttall  (2000)  J Biol Chem  275, 16007-16014  "Potent and selective nonpeptide inhibitors of caspases 3 and 7 inhibit apoptosis and maintain cell functionality"
     
115. J. J. Pan, S. T. Chiou and P. H. Liang  (2000)  Biochemistry  39, 10936-10942  "Product distribution and pre-steady-state kinetic analysis of Escherichia coli undecaprenyl pyrophosphate synthase reaction"
     
116. Jian Dong , Lusong Luo , Po-Huang Liang , Debra Dunaway-Mariano , Paul R. Carey *  (2000)  JOURNAL OF RAMAN SPECTROSCOPY  31, 365-371  "Raman difference spectroscopic studies of dithiobenzoyl substrate and product analogs binding to the enzyme dehalogenase:ppi-electron polarization is prevented by the C=O to C=S substitution."
     
117. A. Sachpatzidis, C. Dealwis, J. B. Lubetsky, P. H. Liang, K. S. Anderson and E. Lolis  (1999)  Biochemistry  38, 12665-12674  "Crystallographic Studies of Phosphonat-Based alpha-reaction transition-State Analogues Complexed to Tryptophan Synthase"
     
118. P. H. Liang, J. Lewis, K. S. Anderson, A. Kohen, F. W. D’Souza, Y. Benenson and T. Bassov  (1998)  Biochemistry  37, 16390-16399  "Catalytic Mechanism of Kdo8P Synthase: Transient Kinetic Studies and Evaluation of a Putative Reaction Intermediate"
     
119. P. H. Liang and K. S. Anderson  (1998)  Biochemistry  37, 12206-12212  "Kinetic Reaction Scheme for the Dihydrofolate Reductase Domain of the Bifunctional Thymidylate Synthase - Dihydrofolate Reductase from Leishmania Major"
     
120. J. Luba, B. Nare, P. H. Liang, K. S. Anderson, S. M. Beverley and L. W. Hardy  (1998)  Biochemistry  37, 4093-4104  "Leishmania Major Pteridine Reductase 1 Belongs to the Short Chain Dehydrogenase Family: Stereochemical and Kinetic Evidence"
     
121. T. R. Schneider, E. Gerhardt, M. Lee, P. H. Liang, K. S. Anderson and I. Schlichting  (1998)  Biochemistry  37, 5394-5406  "Loop Closure and Intersubunit Communication in Tryptophan Synthase"
     
122. P. H. Liang, K. A. Brun, J. A. Field, K. O’Donnell, M. L. Doyle, S. M. Green, A. E. Baker, M. N. Blackburn and S. S. Abdel-Meguid  (1998)  Biochemistry  37, 5923-5929  "Site-Directed Mutagenesis Probing the Catalytic Role of Arginines 165 and 166 of Human Cytomegalovirus Protease"
     
123. P. H. Liang and K. S. Anderson  (1998)  Biochemistry  37, 12195-12205  "Substrate Channeling and Domain-Domain Interactions in Bifunctional Thymidylate Synthase - Dihydrofolate Reductase"
     
124. P. H. Liang, A. Kohen, T. Baasov T and K. S. Anderson  (1997)  Bioorg Med Chem Lett  7, 2463-2468  "Catalytic Mechanism of KDO8P Synthase, Pre-Steady-State Kinetic Analysis Using Rapid Chemical Quench Flow Methods"
     
125. D. E. Cane, H. T. Chiu, P. H. Liang and K. S. Anderson  (1997)  Biochemistry  36, 8332-8339  "Pre-Steady-State Kinetic Analysis of the Trichodiene Synthase Reaction Pathway"
     
126. K. L. Taylor, R. Q. Liu, P. H. Liang, J. Price, D. Dunaway-Mariano, P. J. Tonge, J. Clarkson and P. R. Carey  (1995)  Biochemistry  34, 13881-13888  "Evidence for Electrophilic Catalysis in the 4-Chlorobenzoyl-CoA Dehalogenase Reaction: UV, Raman and C-13 NMR Spectral Studies of Dehalogenase Complexes of Benzoyl-CoA Adducts"
     
127. R. Q. Liu, P. H. Liang, J. D. Scholten and D. Dunaway-Mariano  (1995)  J Am Chem Soc  117, 5003-5004  "Transient State Kinetic Analysis of the Chemical Intermediate Formed in the Enzymatic Dehalogenation of 4-Chlorobenzoyl Coenzyme A"
     
128. G. Yang, P.H. Liang and D. Dunaway-Mariano  (1994)  Biochemistry  33, 8527-8531  "Evidence for Nucleophilic Catalysis in the Aromatic Substitution Reaction Catalyzed by (4-Chlorobenzoyl) coenzyme A dehalogenase"
     
129. P. H. Liang, G. Yang and D. Dunaway-Mariano  (1993)  Biochemistry  32, 12245-12250  "Specificity of 4-chlorobenzoate-Coenzyme A dehalogenase catalyzed dehalogenation of halogenated aromatics"
     
130. P. C. Babbitt, G. L. Kenyon, B. M. Martin, H. Charest, M. Sylvester, J. D. Scholten, K. H. Chang, P. H. Liang and D. Dunaway-Mariano  (1992)  Biochemistry  31, 5594-5604  "Ancestry of the 4-chlorobenzoate dehalogenase: Analysis of amino acid sequence identities among families of acyl: adenyl ligase, enoyl-CoA hydratase/isomerase, and acyl-CoA thioesterase"
     
131. K. H. Chang, P. H. Liang, W. Beck, J. D. Scholten and D. Dunaway-Mariano  (1992)  Biochemistry  31, 5605-5610  "Isolation and characterization of the three polypeptide components of 4-chlorobenzoate dehalogenase from Pseudomonas sp. Strain CBS-3"