中央研究院 生物化學研究所

研究領域與專長

專長

1. 蛋白質X-光結晶學
2. 同步輻射X-光繞射數據收集
3. 結構生物學
4. 以蛋白質結構為基礎的藥物最佳化
5. 以結構為基礎的蛋白質分析

研究

• 以蛋白質結構為基礎的小分子藥物開發、設計及最佳化，以治療神經退化性疾病

學經歷

• 2002 – 2006   博士, 生化科學研究所, 國立臺灣大學
• 1991 – 1993   碩士, 生化科學研究所, 國立臺灣大學
• 1986 – 1991   學士, 獸醫學系, 國立中興大學

• 2017 – 迄今   研究技師, 中研院生化所
• 2016 – 迄今   計畫總經理, 台灣蛋白質計畫
• 2013 – 2017   研究副技師, 中研院生化所
• 2011 – 2015   計畫經理, 國家蛋白質結構分析核心設施
• 2009 – 2012   研究助技師, 中研院生化所
• 2005 – 2011   計畫經理, 國家蛋白質生產及X-光結晶學核心設施
• 1993 – 2009   研究助理, 中研院生化所

主要著作

Structural basis for fragmenting the exopolysaccharide of Acinetobacter baumannii by bacteriophage ΦAB6 tailspike protein. 
Lee, I.-M., Tu, I.-F., Yang, F.-L., Ko, T.-P., Liao, J.-H., Lin, N.-T., Wu, C.-Y., Ren, C.-T., Wang, A. H.-J., Chang, C.-M., Huang, K.-F. & Wu, S.-H. 
Scientific Reports (2017)

A multivalent marine lectin from Crenomytilus grayanus possesses anti-cancer activity through recognizing globotriose Gb3. 
Liao, J.-H., Chien, C.-T., Wu, H.-Y., Huang, K.-F., Wang, I., Ho, M.-R., Tu, I.-F., Lee, I.-M., Li, W., Shih, Y.-L., Wu, C.-Y., Lukyanov, P.-A., Hsu, S.-T. & Wu, S.-H. 
Journal of the American Chemical Society (2016)

Avenaciolides: potential MurA-targeted inhibitors against peptidoglycan biosynthesis in methicillin-resistant Staphylococcus aureus (MRSA). 
Chang, C.-M., Chern, J., Chen, M.-Y., Huang, K.-F., Chen, C.-H., Yang, Y.-L. & Wu, S.-H. 
Journal of the American Chemical Society (2015)

Linked production of pyroglutamate-modified proteins via self-cleavage of fusion tags with TEV protease and autonomous N-terminal cyclization with glutaminyl cyclase in vivo. 
Shih, Y.-P., Chou, C.-C., Chen, Y.-L., Huang, K.-F. & Wang, A. H.-J. 
PLoS One (2014)

Structural and functional analyses of a glutaminyl cyclase from Ixodes scapularis reveal metal-independent catalysis and inhibitor binding. 
Huang, K.-F., Hsu, H.-L., Karim, S. & Wang, A. H.-J. 
Acta Crystallographica Section D Biological Crystallography (2014)

Structures of human Golgi-resident glutaminyl cyclase and its complexes with inhibitors reveal a large loop movement upon inhibitor binding. 
Huang, K.-F., Liaw, S.-S., Huang, W.-L., Chia, C.-Y., Lo, Y.-C., Chen, Y.-L. & Wang, A. H.-J. 
Journal of Biological Chemistry (2011)

Crystal Structure and Functional Analysis of the Glutaminyl Cyclase from Xanthomonas campestris. (Featured on Cover) 
Huang, W.-L., Wang, Y.-R., Ko, T.-P., Chia, C.-Y., Huang, K.-F. & Wang, A. H.-J. 
Journal of Molecular Biology (2010)

A conserved hydrogen-bond network in the catalytic centre of animal glutaminyl cyclases is critical for catalysis. 
Huang, K.-F., Wang, Y.-R., Chang, E.-C., Chou, T.-L. & Wang, A. H.-J. 
The Biochemical journal (2008)

Crystal structures of human glutaminyl cyclase, an enzyme responsible for protein N-terminal pyroglutamate formation. 
Huang, K.-F., Liu, Y.-L., Cheng, W.-J., Ko, T.-P. & Wang, A. H.-J. 
Proceedings of the National Academy of Sciences of the United States of America (2005)

Crystal structure of a platelet-agglutinating factor isolated from the venom of Taiwan habu (Trimeresurus mucrosquamatus). (Featured on Cover) 
Huang, K.-F., Ko, T.-P., Hung, C.-C., Chu, J., Wang, A. H.-J. & Chiou, S.-H. 
The Biochemical Journal (2004)

著作列表

1. Maestre-Reyna M, Yang CH, Nango E, Huang WC, Ngurah Putu EPG, Wu WJ, Wang PH, Franz-Badur S, Saft M, Emmerich HJ, Wu HY, Lee CC, (Huang KF), Chang YK, Liao JH, Weng JH, Gad W, Chang CW, Pang AH, Sugahara M, Owada S, Hosokawa Y, Joti Y, Yamashita A, Tanaka R, Tanaka T, Luo F, Tono K, Hsu KC, Kiontke S, Schapiro I, Spadaccini R, Royant A, Yamamoto J, Iwata S, Essen LO*, Bessho Y*, Tsai MD*  (2022-06)  Nature chemistry  14(6), 677-685  "Serial crystallography captures dynamic control of sequential electron and proton transfer events in a flavoenzyme."
   
2. Lin CC, Hoo SY, Ma LT, Lin C, (Huang KF), Ho YN, Sun CH, Lee HJ, Chen PY, Shu LJ, Wang BW, Hsu WC, Ko TP, Yang YL  (2022-05)  Communications biology  5(1), 454  "Integrated omics approach to unveil antifungal bacterial polyynes as acetyl-CoA acetyltransferase inhibitors."
   
3. Ye TJ, (Huang KF), Ko TP, Wu SH  (2022-05)  Acta Crystallographica Section D-Structural Biology  78(Pt 5), 633-646  "Synergic action of an inserted carbohydrate-binding module in a glycoside hydrolase family 5 endoglucanase."
   
4. Tu IF, Lin TL, Yang FL, Lee IM, Tu WL, Liao JH, Ko TP, Wu WJ, Jan JT, Ho MR, Chou CY, Wang AH, Wu CY, Wang JT, (Huang KF)*, Wu SH*  (2022-02)  Journal of Biomedical Science  29(1), 9  "Structural and biological insights into Klebsiella pneumoniae surface polysaccharide degradation by a bacteriophage K1 lyase: implications for clinical use."
   
5. Li S, Hsieh KY, Kuo CI, Su SC, (Huang KF), Zhang K, Chang CI  (2021-11)  Science Advances  7(46), eabj9537  "Processive cleavage of substrate at individual proteolytic active sites of the Lon protease complex."
   
6. Tsai IH*, Wang YM, Lin SW, (Huang KF)  (2021-07)  Toxicon  198, 93-101  "Structural and bioinformatic analyses of Azemiops venom serine proteases reveal close phylogeographic relationships to pitvipers from eastern China and the New World"
   
7. Chen ST, Liao JH, (Huang KF), Lee IM, Wong WT, Wu SH*, Hua KF*  (2021-06)  Chemical Communications  57(50), 6209-6212  "A GalNAc/Gal-specific lectin modulates immune responses via toll-like receptor 4 independently of carbohydrate-binding ability."
   
8. (Huang KF)*, Huang JS, Wu ML, Hsieh WL, Hsu KC, Hsu HL, Ko TP, Wang AH*  (2021-06)  Journal of Molecular Biology  433(13), 166960  "A unique carboxylic-acid hydrogen-bond network (CAHBN) confers glutaminyl cyclase activity on M28 family enzymes."
   
9. Khine AA, Lu PC, Ko TP, (Huang KF), Chen HP  (2020-11)  Protein expression and purification  175, 105715  "Cloning, expression, identification and characterization of borneol dehydrogenase isozymes in Pseudomonas sp. TCU-HL1."
   
10. Khine AA, Chen HP, (Huang KF)*, Ko TP*  (2020-07)  Acta Crystallographica Section F-Structural Biology Communications  76(Pt 7), 309-313  "Structural characterization of borneol dehydrogenase from Pseudomonas sp. TCU-HL1."
    
11. Ko KT, Hu IC, (Huang KF), Lyu PC, Hsu SD  (2019-08)  Structure  27(8),1224-1233  "Untying a Knotted SPOUT RNA Methyltransferase by Circular Permutation Results in a Domain-Swapped Dimer."
    
12. Chang HY, Ko TP, Chang YC, (Huang KF), Lin CY, Chou HY, Chiang CY, Tsai HJ  (2019-06)  International journal of biological macromolecules  130, 675-684  "Crystal structure of the blue fluorescent protein with a Leu-Leu-Gly tri-peptide chromophore derived from the purple chromoprotein of Stichodactyla haddoni."
    
13. Chen ES, Weng JH, Chen YH, Wang SC, Liu XX, Huang WC, Matsui T, Kawano Y, Liao JH, Lim LH, Bessho Y, (Huang KF), Wu WJ, Tsai MD  (2017-09)  Biochemistry  56(38), 5112-5124  "Phospho-Priming Confers Functionally Relevant Specificities for Rad53 Kinase Autophosphorylation."
    
14. 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."
    
15. Chou CC, Modi JP, Wang CY, Hsu PC, Lee YH, (Huang KF), Wang AH, Nan C, Huang X, Prentice H, Wei J, Wu JY  (2017-03)  Molecular neurobiology  54(2), 866-873  "Activation of Brain L-glutamate Decarboxylase 65 Isoform (GAD65) by Phosphorylation at Threonine 95 (T95)."
    
16. Lee IM, Tu IF, Yang FL, Ko TP, Liao JH, Lin NT, Wu CY, Ren CT, Wang AH, Chang CM, (Huang KF)*, Wu SH*  (2017-02)  Scientific reports  7, 42711  "Structural basis for fragmenting the exopolysaccharide of Acinetobacter baumannii by bacteriophage PhiAB6 tailspike protein."
    
17. Chang HY, Lin ST, Ko TP, Wu SM, Lin TH, Chang YC, (Huang KF), Lee TM  (2017)  Plant physiology and biochemistry : PPB  120, 144-155  "Enzymatic characterization and crystal structure analysis of Chlamydomonas reinhardtii dehydroascorbate reductase and their implications for oxidative stress."
    
18. Tsang HL, Huang JL, Lin YH, (Huang KF), Lu PL, Lin GH, Khine AA, Hu A, Chen HP  (2016-10)  Applied and environmental microbiology  82(21), 6378-6385  "Borneol Dehydrogenase from Pseudomonas sp. Strain TCU-HL1 Catalyzes the Oxidation of (+)-Borneol and Its Isomers to Camphor."
    
19. Hou SC, Chen HS, Lin HW, Chao WT, Chen YS, Fu CY, Yu CM, (Huang KF), Wang AH, Yang AS  (2016-08)  Scientific reports  6, 31878  "High throughput cytotoxicity screening of anti-HER2 immunotoxins conjugated with antibody fragments from phage-displayed synthetic antibody libraries."
    
20. Tsai IH, Wang YM, (Huang KF)  (2016-05)  Toxicon  114, 31-39  "Structures of Azemiops feae venom phospholipases and Cys-rich-secretory protein and implications for taxonomy and toxinology."
    
21. Liao JH, Chien CT, Wu HY, (Huang KF), Wang I, Ho MR, Tu IF, Lee IM, Li W, Shih YL, Wu CY, Lukyanov PA, Hsu ST, Wu SH  (2016-04)  Journal of the American Chemical Society  138(14), 4787-4795  "A Multivalent Marine Lectin from Crenomytilus grayanus Possesses Anti-cancer Activity through Recognizing Globotriose Gb3."
    
22. Weng JH, Hsieh YC, Huang CC, Wei TY, Lim LH, Chen YH, Ho MR, Wang I, (Huang KF), Chen CJ, Tsai MD  (2015-10)  Biochemistry  54(40), 6219-6229  "Uncovering the Mechanism of Forkhead-Associated Domain-Mediated TIFA Oligomerization That Plays a Central Role in Immune Responses."
    
23. Hsieh JF, Lin WJ, (Huang KF), Liao JH, Don MJ, Shen CC, Shiao YJ, Li WT  (2015-03)  European journal of medicinal chemistry  93, 443-451  "Antioxidant activity and inhibition of alpha-glucosidase by hydroxyl-functionalized 2-arylbenzo[b]furans."
    
24. Chang CM, Chern J, Chen MY, (Huang KF), Chen CH, Yang YL, Wu SH  (2015-01)  Journal of the American Chemical Society  137(1), 267-275  "Avenaciolides: Potential MurA-Targeted Inhibitors Against Peptidoglycan Biosynthesis in Methicillin-Resistant Staphylococcus aureus (MRSA)."
    
25. Tsai IH, Wang YM, (Huang KF)  (2015-01)  Toxicon  94, 50-59  "Effects of single N-glycosylation site knockout on folding and defibrinogenating activities of acutobin recombinants from HEK293T."
    
26. Wang YM, (Huang KF), Tsai IH  (2014-08)  Toxicon  86, 40-50  "Snake venom glutaminyl cyclases: Purification, cloning, kinetic study, recombinant expression, and comparison with the human enzyme."
    
27. Liao JH, Lin IL, (Huang KF), Kuo PT, Wu SH, Wu TH  (2014)  Journal of agricultural and food chemistry  62(25), 5932-5938  "Carnosine ameliorates lens protein turbidity formations by inhibiting calpain proteolysis and ultraviolet C-induced degradation."
    
28. Shih YP, Chou CC, Chen YL, (Huang KF)*, Wang AH*  (2014)  PloS one  9(4), e94812  "Linked Production of Pyroglutamate-Modified Proteins via Self-Cleavage of Fusion Tags with TEV Protease and Autonomous N-Terminal Cyclization with Glutaminyl Cyclase In Vivo."
    
29. (Huang KF)*, Hsu HL, Karim S, Wang AH*  (2014)  Acta Crystallographica Section D-Biological Crystallography  70(Pt 3), 789-801  "Structural and functional analyses of a glutaminyl cyclase from Ixodes scapularis reveal metal-independent catalysis and inhibitor binding."
    
30. Chou TL, Wu CH, (Huang KF)*, Wang AH*  (2013)  Toxicon : official journal of the International Society on Toxinology  71, 140-146  "Crystal structure of a Trimeresurus mucrosquamatus venom metalloproteinase providing new insights into the inhibition by endogenous tripeptide inhibitors."
    
31. Liao JH, Ihara K, Kuo CI, (Huang KF), Wakatsuki S, Wu SH, Chang CI  (2013)  ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY  69(Pt 8), 1395-1402  "Structures of an ATP-independent Lon-like protease and its complexes with covalent inhibitors."
    
32. Li JK, Liao JH, Li H, Kuo CI, (Huang KF), Yang LW, Wu SH, Chang CI  (2013)  ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY  69(Pt 9), 1789-1797  "The N-terminal substrate-recognition domain of a LonC protease exhibits structural and functional similarity to cytosolic chaperones."
    
33. Chen YL, (Huang KF), Kuo WC, Lo YC, Lee YM, Wang AH  (2012-03)  Biochemical journal  442(2), 403-412  "Inhibition of Glutaminyl Cyclase Attenuates Cell Migration Modulated by Monocyte Chemoattractant Proteins."
    
34. Chen HS, Wang YM, Huang WT, (Huang KF), Tsai IH  (2012-02)  Biochimie  94(2), 335-344  "Cloning, characterization and mutagenesis of Russell's viper venom l-amino acid oxidase: Insights into its catalytic mechanism."
    
35. Yu CM, Peng HP, Chen IC, Lee YC, Chen JB, Tsai KC, Chen CT, Chang JY, Yang EW, Hsu PC, Jian JW, Hsu HJ, Chang HJ, Hsu WL, (Huang KF), Ma AC, Yang AS  (2012)  PloS one  7(3), e33340  "Rationalization and design of the complementarity determining region sequences in an antibody-antigen recognition interface."
    
36. Wu HH, Wu PY, (Huang KF), Kao YY, Tsai MD  (2012)  Biochemistry  51(2), 575-577  "Structural delineation of MDC1-FHA domain binding with CHK2-pThr68."
    
37. Chou CY, Ko TP, Wu KJ, (Huang KF), Lin CH, Wong CH, Wang AH  (2011)  JOURNAL OF BIOLOGICAL CHEMISTRY  286(16), 14057-14064  "Modulation of Substrate Specificities of D-Sialic Acid Aldolase through Single Mutations of Val-251."
    
38. (Huang KF), Liaw SS, Huang WL, Chia CY, Lo YC, Chen YL, Wang AH  (2011)  JOURNAL OF BIOLOGICAL CHEMISTRY  286(14), 12439-12449  "Structures of human Golgi-resident glutaminyl cyclase and its complexes with inhibitors reveal a large loop movement upon inhibitor binding."
    
39. Shih YL, (Huang KF), Lai HM, Liao JH, Lee CS, Chang CM, Mak HM, Hsieh CW, Lin CC  (2011)  PloS one  6(6), e21425  "The N-Terminal Amphipathic Helix of the Topological Specificity Factor MinE Is Associated with Shaping Membrane Curvature."
    
40. Huang WL, Wang YR, Ko TP, Chia CY, (Huang KF)*, Wang AH*  (2010-08)  Journal of molecular biology  401(3), 374-388  "Crystal Structure and Functional Analysis of the Glutaminyl Cyclase from Xanthomonas campestris."
    
41. Huang, K.-F., Wang, Y.-R., Chang, E.-C., Chou, T.-L. & Wang, A. H.-J.  (2008)  The Biochemical journal  411(1), 181-190  "A conserved hydrogen-bond network in the catalytic centre of animal glutaminyl cyclases is critical for catalysis."
    
42. Chin, K.-H., Tsai, Y.-D., Chan, N.-L., Huang, K.-F., Wang, A. H.-J. & Chou, S.-H.  (2007)  Proteins  69(3), 665-671  "The crystal structure of XC1258 from Xanthomonas campestris: a putative procaryotic Nit protein with an arsenic adduct in the active site."
    
43. Huang, K.-F., Liu, Y.-L. & Wang, A. H.-J.  (2005)  Protein expression and purification  43(1), 65-72  "Cloning, expression, characterization, and crystallization of a glutaminyl cyclase from human bone marrow: a single zinc metalloenzyme."
    
44. Huang, K.-F., Liu, Y.-L., Cheng, W.-J., Ko, T.-P. & Wang, A. H.-J.  (2005)  Proceedings of the National Academy of Sciences of the United States of America  102(37), 13117-13122  "Crystal structures of human glutaminyl cyclase, an enzyme responsible for protein N-terminal pyroglutamate formation."
    
45. Huang, K.-F., Ko, T.-P., Hung, C.-C., Chu, J., Wang, A. H.-J. & Chiou, S.-H.  (2004)  The Biochemical journal  378(Pt 2), 399-407  "Crystal structure of a platelet-agglutinating factor isolated from the venom of Taiwan habu (Trimeresurus mucrosquamatus)."
    
46. Huang, K.-F., Chiou, S.-H., Ko, T.-P. & Wang, A.H.-J.  (2002)  European journal of biochemistry / FEBS  269(12), 3047-3056  "Determinants of the inhibition of a Taiwan habu venom metalloproteinase by its endogenous inhibitors revealed by X-ray crystallography and synthetic inhibitor analogues."
    
47. Huang, K.-F., Chiou, S.-H., Ko, T.-P., Yuann, J.-M. & Wang, A. H.-J.  (2002)  Acta Crystallographica Section D-Biological Crystallography  58(Pt 7), 1118-1128  "The 1.35 A structure of cadmium-substituted TM-3, a snake-venom metalloproteinase from Taiwan habu: elucidation of a TNFalpha-converting enzyme-like active-site structure with a distorted octahedral geometry of cadmium."
    
48. Huang, K.-F., Chow, L.-P. & Chiou, S.-H.  (1999)  Biochemical and biophysical research communications  263(3), 610-616  "Isolation and characterization of a novel proteinase inhibitor from the snake serum of Taiwan habu (Trimeresurus mucrosquamatus)."
    
49. Huang, K.-F., Hung, C.-C., Wu, S.-H. & Chiou, S.-H.  (1998)  Biochemical and biophysical research communications  248(3), 562-568  "Characterization of three endogenous peptide inhibitors for multiple metalloproteinases with fibrinogenolytic activity from the venom of Taiwan habu (Trimeresurus mucrosquamatus)."
    
50. Chiou, S.-H., Huang, K.-F., Chow, L.-P., Tsugita, A. & Wu, S.-H.  (1996)  Journal of protein chemistry  15(7), 667-674  "Isolation of a venom factor devoid of proteolytic activity from Taiwan habu (Trimeresurus mucrosquamatus): N-terminal sequence homology and no functional similarity to factors IX/X-binding proteins and botrocetin."
    
51. Huang, K.-F., Hung, C.-C., Pan, F.-M., Chow, L.-P., Tsugita, A. & Chiou, S.-H.  (1995)  Biochemical and biophysical research communications  216(1), 223-233  "Characterization of multiple metalloproteinases with fibrinogenolytic activity from the venom of Taiwan habu (Trimeresurus mucrosquamatus): protein microsequencing coupled with cDNA sequence analysis."
    
52. Hung, C.-C., Huang, K.-F. & Chiou, S.-H.  (1994)  Biochemical and Biophysical Research Communications  205(3), 1707-1715  "Characterization of one novel venom protease with beta-fibrinogenase activity from the Taiwan habu (Trimeresurus mucrosquamatus): purification and cDNA sequence analysis."
    
53. Huang, K.-F., Hung, C.-C. & Chiou, S.-H.  (1993)  Biochemistry and Molecular Biology International  31(6), 1041-1050  "Characterization of three fibrinogenolytic proteases isolated from the venom of Taiwan habu (Trimeresurus mucrosquamatus)."
    
54. Chang, C.-C., Huang, T.-Y., Kuo, K.-W., Chen, S.-W., Huang, K.-F. & Chiou, S.-H.  (1993)  Biochemical and Biophysical Research Communications  191(1), 214-223  "Sequence characterization of a novel alpha-neurotoxin from the king cobra (Ophiophagus hannah) venom."
    
55. Chiou, S.-H., Hung, C.-C. & Huang, K.-F.  (1992)  Biochemical and biophysical research communications  187(1), 389-396  "Characterization of a protease with alpha- and beta-fibrinogenase activity from the Western diamondback rattlesnake, Crotalus atrox."