在此論文中將討論臺灣眼鏡蛇毒素V與醣胺素衍生雙醣的交互作用。心臟毒素有毒殺細胞的作用，且能造成大範圍的發炎反應與組織壞死。而醣胺素是心臟蛇毒的可能目標以標定欲攻擊的特定細胞。
心臟毒素V為相當特異的同源心臟毒素之一，在指環I與指環II的變異使得它表現對於脂質以及醣胺素有較高的親合力，毒性變低，且至今未發現它真正的目標。我們的結果顯示，心臟毒素V與醣胺素的結合可能是經由指環II來結合，由蛋白NOE連結的訊號改變，推測其局部的構形改變，並由auto-docking與x-ray結晶的多餘電子密度，也初步證實了由指環II結合的結果。與先前的心臟蛇毒III與雙醣結合的結構比較，心臟毒素V擁有一個全新的結合位置。且心臟毒素V也會對於醣胺素上不同的硫化區域，表現不同的親合力。這些數據顯示了不同的心臟毒素對醣胺素有不同的結合位置，而肝素上的硫化區域，也對結合有決定性的影響，此結果也表示了心臟毒素V對醣的辨示能力。

In this thesis,we are going to investigate the interaction of the heparinderived disaccharide with the cardiotoxin V (CTX A5). Cardiotoxinswill envenom the target cells and might cause severe necrosis and inflammation ,and glycosaminoglycan serve as potential target within
the process. The distinct loop regions of CTX A5 differs by two inserts and mutations on the loop I and II make it exhibit much higher affinity to glycosaminoglycans and lipids than other cardiotoxin homologues.
From our result of auto-docking and the preliminary x-ray structure suggest the binding of heparin derived disaccharide to CTX A5 is through loop II region and induces protein local conformation change. Compared
with the former complex structure CTX A3, CTX A5 complex shows a novel binding site which is consist with the long-chain heparin SPR data. And the binding specificities is proven to depend on the sulfation motif of the disaccharide, thus suggest recognition of CTX A5 to
glycosaminoglycans.

[1] Wen-guey Wu. Cobra Cardiotoxin and Phospholipase A2 as GAGbinding
Toxins:On the Path from Structure to Cardiotoxicity and
Inflammation. TCM, 1998, 8, 270–278.
[2] Zhang, L. ; Rozek, A. ; Hancock, R. E. Interaction of Cationic Antimicrobial
Peptides with Model Membranes.J. Biol. Chem. 2001,
276, 25714–35722.
[3] Chien-Min Chiang, Shou-Lin Chang, Hai-jui Lin, and Wen-guey
Wu. The Role of Acidic Amino Acid Residues in the Structural Stability
of Snake Cardiotoxins. Biochemistry, 1996, 35, 9177–9186.
[4] Yuh-Ju Sun; Wen-guey Wu; Chien-Min Chiang; A-Yen Hsin; and
Chwan-Deng Hsiao. Crystal Structure of Cardiotoxin V from Taiwan
Cobra Venom: pH-Dependent Conformational Change and
a Novel Membrane-Binding Motif Identified in the Three-Finger
Loops of P-Type Cardiotoxin. Biochemistry, 1997, 36, 2403–2413.
[5] Rex S. and Schwarz, G. Quantitative Studies on the Melittin-
Induced Leakage Mechanism of Lipid Vesicles. Biochemistry, 1998,
37, 2336–2345.
[6] Markin, V. and Albanes, J. P. Membrane Fusion: stalk model
revisited.Biophys. J. 2002, 82, 639–712.
[7] Souhei Mizuguchi; Toru Uyama; Hiroshi Kitagawa; Kazuko H.
Nomura; Katsufumi Dejima; Keiko Gengyo-Ando; Shohei Mitani;
Kazuyuki Sugahara; Kazuya Nomura. Chondroitin Proteoglycans
Are Involved in Cell Division of Caenorhabditis Elegans. Nature
2003, 423, 443–448.
[8] Peter Teriete; Suneale Banerji; Martin Noble; Charles D. Blundell;;
Alan J. Wright; Andrew R. Pickford; Edward Lowe; David J.
Mahoney; Markku I. Tammi Jan D. Kahmann; Iain D. Campbell;
Anthony J. Day;; and David G. Jackson. Structure of the Regulatory
Hyaluronan Binding Domain in the Inflammatory Leukocyte
Homing Receptor CD44. Molecular Cell, 2004, 13, 483–496.
[9] V. S. Raghavendra Rao et al. “Conformation of Carbohydrates.”
Published by harwood academic publishers. Available at Library
of Academia Sinica, Taiwan.
105
[10] Himatkumar V. Patel; Alka A. Vyas; Kavita A. Vyas; Yi-Shiuan
Liu; Chien-Min Chiang; Lang-Ming Chi; and Wen-guey Wu. Heparin
and Heparan Sulfate Bind to Snake Cardiotoxin. J. Biol.
Chem. 1997, 272, 1484–1492.
[11] Shih-Che Sue; Jean-Robert Brisson; Siu-Cin Chang; Wei-Ning
Huang; Shao-Chen Lee; Harold C. Jarrell; and Wen-guey Wu.
Structures of Heparin-Derived Disaccharide Bound to Cobra Cardiotoxins:
Context-Dependent Conformational Change of Heparin
upon Binding to the Rigid Core of the Three-Fingered Toxin. Biochemistry,
2001, 40, 10436–10446.
[12] Dirk Henrichsen; Beat Ernst; John L. Magnani; Wei-Tong Wang;
Bernd Meyer; Thomas Peters. Bioaffinity NMR Spectroscopy:
Identification of an E-Selectin Antagonist in a Substance Mixture
by Transfer NOE. Angew. Chem. Int. Ed. 1999, 38, 98–102.
[13] Moriz Mayer; Bernd Meyer. Characterization of Ligand Binding by
Saturation Transfer Difference NMR Spectroscopy. Angew. Chem.
Int. Ed. 1999, 38, 1784–1788.
[14] Diaz, M. Dolores ; Berger, Stefan. Studies of the Complexation of
Sugars by Diffusion-ordered NMR Spectroscopy. Carbohydra. Res.
2000, 329, 1–5.
[15] Tomati, Umberto; Belardinelli, Monica; Galli, Emanuela; Iori,
Valentina; Capitani, Donatella; et. al. NMR Characterization of
the Polysaccharidic Fraction from Lentinula edodes Grown on
Olive Mill Waste Waters. Carbohydra. Res. 2004, 339, 1129–1134.
[16] Amanda S. Altieri, Denise P. Hinton, R. Andrew Byrd. Association
of Biomolecular Systems via Pulsed Field Gradient NMR
Self-Diffusion Measurements. J. Am. Chem. Soc. 1995, 117, 7566–
7567.
[17] Eads, C. D. ; Noda, I. Generalized Correlation NMR Spectroscopy.
J. Am. Chem. Soc. 2002, 124, 1111–1118.
[18] Hiroyuki Saito; Padmaja Dhanasekaran; David Nguyen; Faye
Baldwin; Karl H.Weisgraber; SuzanneWehrli; Michael C. Phillips;
and Sissel Lund-Katz. Characterization of the Heparin Binding
Sites in Human Apolipoprotein E. J. Biol. Chem. 2003, 278,
14782–14787.
[19] Sachchidanand; Olivier Lequin; David Staunton; Barbara Mulloy;
Mark J. Forster; Keiichi Yoshida; and Iain D. Campbell. Mapping
the Heparin-binding Site on the 13-14F3 Fragment of Fibronectin.
J. Biol. Chem. 2003, 277, 50629–50635.
[20] Barjat; Herve; Morris; Gareth A. ; Swanson; Alistair G. A Three-
Dimensional DOSY–HMQC Experiment for the High-Resolution
Analysis of Complex Mixtures. J. Magn. Reson. 1998, 131, 131–
138.
106
[21] Loening, Nikolaus M. ; Keeler, James; Morris, Gareth A. One-
Dimensional DOSY. J. Magn. Reson. 2001, 153, 103–112.
[22] Lucas, Laura H. ; Otto, William H. ; Larive, Cynthia K. The 2D-JDOSY
Experiment: Resolving Diffusion Coefficients in Mixtures.
J. Magn. Reson. 2002, 156, 138–145.
[23] Jayalakshmi, V. ; Rama Krishna, N. CORCEMA refinement of the
bound ligand conformation within the protein binding pocket in
reversibly forming weak complexes using STD-NMR intensities. J.
Magn. Reson. 2004, 168, 36–45.
[24] Gozansky, Elliott K. ; Gorenstein, David G. DOSY-NOESY:
Diffusion-Ordered NOESY. J. Magn. Reson. 1996, 111, 94–96.
[25] Akiko Hori; Kazuhisa Kumazawa; Takahiro Kusukawa; Dillip Kumar
Chand; Makoto Fujita; Shigeru Sakamoto; and Kentaro Yamaguchi.
DOSY Study on Dynamic Catenation: Self-Assembly of a
Catenane as a Meta-Stable Compound from Twelve Simple Components.
Chem. Eur. J. 2001, 7, 4142–4149.
[26] Patrick Groves; Martin Ohsten Rasmussen; M. Dolores Molero;
Eric Samain; F. Javier Ca˜nada ; Hugues Driguez and Jes´us
Jim´enez-Barbero; Diffusion Ordered Spectroscopy as a Complement
to Size Exclusion Chromatography in Oligosaccharide Analysis.
Glycobiology 2004, 14, 451–456.
[27] Antonio H. Daranas; Jos´e J. Ferna´ndez; Ezequiel Q. Morales;
Manuel Norte; and Jos´e A. Gavy´n. Self-Association of Okadaic
Acid upon Complexation with Potassium Ion. J. Med. Chem.
2004, 47, 10–13.
[28] Fioroni, M. ; Diaz, M. D. ; Burger, K. ; Berger, S. Solvation
Phenomena of a Tetrapeptide in Water/Trifluoroethanol and Water/
Ethanol Mixtures: A Diffusion NMR, Intermolecular NOE,
and Molecular Dynamics Study. J. Am. Chem. Soc. 2002, 124,
7737–7744.
[29] Rebecca Lever; Clive P. Page. Novel Drug Development Opportunities
for Heparin. Nature Reviews Drug Discovery 2002, 1, 140–
148.
[30] Maurizio Pellecchia; Daniel S. Sem; Kurt W¨uthrich. NMR in Drug
Discovery. Nature Reviews Drug Discovery 2002, 1, 211–219.
[31] Jocelyne Fiaux; Eric B. Bertelsen; Arthur L. Horwich; Kurt
W¨uthrich. NMR Analysis of A 900K GroEL-GroES Complex. Nature
2002, 418, 207–211.
[32] Sarah Tomlin Nuclear Polarization: More Spins for Protons. Nature
2000, 403, 151.
107
[33] Bernd Meyer and Thomas Peters. NMR Spectroscopy Techniques
for Screening and Identifying Ligand Binding to Protein Receptors.
Angew. Chem. Int. Ed. 2003, 42, 864–890.
[34] Ishan Capila; Robert J. Linhardt. Heparin-Protein Interactions.
Angew. Chem. Int. Ed. 2002, 41, 390–412.
[35] Mine, S. ; Yamazaki, T. ; Miyata, T. ; Hara, S. ; Kato, H. Structural
Mechanism for Heparin-Binding of the Third Kunitz Domain
of Human Tissue Factor Pathway Inhibitor. Biochemistry 2002, 41,
78–85.
[36] Johnson, M. A. ; Rotondo, A. ; Pinto, B. M. NMR Studies of the
Antibody-Bound Conformation of a Carbohydrate-Mimetic Peptide.
Biochemistry 2002, 41, 2149–2157.
[37] Johnson, Margaret A. ; Pinto, B. Mario. NMR Spectroscopic and
Molecular Modeling Studies of Protein-Carbohydrate and Protein-
Peptide Interactions. Carbohydra. Res. 2004, 339, 907–928.
[38] Chevalier, Franck; Lucas, Ricardo; Angulo, Jesus; Martin-Lomas,
Manuel; Nieto, Pedro M. The Heparin–Ca2+ Interaction: the In-
fluence of the O-sulfation Pattern on Binding. Carbohydra. Res.
2004, 339, 975–983.
[39] Colombo, Giorgio; Meli, Massimiliano; Canada, Javier; Asensio,
Juan Luis; Jimenez-Barbero, Jes´us Toward the Understanding of
the Structure and Dynamics of Protein-carbohydrate Interactions:
Molecular Dynamics Studies of the Complexes Between Hevein and
Oligosaccharidic Ligands. Carbohydra. Res. 2004, 339, 985–994.
[40] Medek, A. ; Hajduk, P. J. ; Mack, J. ; Fesik, S. W. The Use
of Differential Chemical Shifts for Determining the Binding Site
Location and Orientation of Protein-Bound Ligands. J. Am. Chem.
Soc. 2000, 122, 1241–1242.
[41] Kuhn LA; Griffin JH; Fisher CL; Greengard JS; Bouma BN; Espana
F; Tainer JA. Elucidating the Structural Chemistry of Glycosaminoglycan
Recognition by Protein C Inhibitor. Proc. Natl.
Acad. Sci. , 199, 21, 8506–8510.
[42] Liu S; Zhou F; Hook M; Carson DD. A Heparin-Binding Synthetic
Peptide of Heparin/Heparan Sulfate-Interacting Protein Modulates
Blood Coagulation Activities. Proc. Natl. Acad. Sci. , 1997,
94, 1739–1744.
[43] Michael Gottschalk; Kandadai Venu; and Bertil Halle. Protein
Self-Association in Solution: The Bovine Pancreatic Trypsin Inhibitor
Decamer. Biophysical Journal 2003, 84, 3941–3958.
108
[44] Zuccaccia, C. ; Stahl, N. G. ; Macchioni, A. ; Chen, M. -C. ;
Roberts, J. A. ; Marks, T. J. NOE and PGSE NMR Spectroscopic
Studies of Solution Structure and Aggregation in Metallocenium
Ion-Pairs. J. Am. Chem. Soc. 2004, 126, 1448–1464.
[45] Hajduk, P. J. ; Mack, J. C. ; Olejniczak, E. T. ; Park, C. ; Dandliker,
P. J. ; Beutel, B. A. SOS-NMR: A Saturation TransferNMRBased
Method for Determining the Structures of Protein-Ligand
Complexes. J. Am. Chem. Soc. 2004, 126, 2390–2398.
[46] Markley, John L. ; Bax, Ad; Arata, Yoji; Hilbers, C. W. ; Kaptein,
Robert; Sykes, Brian D. ; Wright, Peter E. and Kurt W¨uthrich.
Recommendations for the Presentation of NMR Structures of Proteins
and Nucleic Acids.
[47]
Ê
CÉiŸƒ-DƒÖ A3Dòv“ý
"Öµ‾Ó X-ray 3D
!Z ÀM×çî=d, 2004.
[48] Huang, C. C. , Couch, G. S. , Pettersen, E. F. , and Ferrin, T.
E.`‘Chimera: An Extensible Molecular Modeling Application Constructed
Using StandardComponents.“ Pacific Symposium on Biocomputing1996,
1:724 . http://www.cgl.ucsf.edu/chimera.
[49] T. D. Goddard and D. G. Kneller, SPARKY 3, University of California,
San Francisco.
[50] Peter G¨untert, Christian Mumenthaler and Torsten Herrmann.
DYANA Manual. Available at web site:
http://gwagner.med.harvard.edu/nmr/wwwsoftlib/cyana/DyanaManual.pdf
[51] Using ”Sparky” to evaluate volumes of peaks in 2-D spectra.
http://www.cm.utexas.edu/hoffman/sparkyintegrate.pdf.
http://www.cm.utexas.edu/hoffman
[52] Herrmann, Torsten; G¨untert, Peter; W¨uthrich. Protein NMR
Structure Determination with Automated NOE Assignment Using
the New Software CANDID and the Torsion Angle Dynamics
Algorithm DYANA. J. Mol. Biol. 2002, 319, 209–227.
[53] Enrico Morelli. 2004. http://www.cerm.unifi.it/Sparky/extension.html.
[54] ÏÏf]t
, www.wjxy.edu.cn/ jpkc/wl/sy/part0/sect03.doc.
[55] ˝2p, 2004, ÀMÞ·çÍÛ±4õð

[56] ±¬ |4°!|Ê-DƒÖ!Z£
º4Š?,5iH ÀM×ç²
=d, 1996.
[57] Chien-Min Chian, Kun-Yi Chien, Hai-jui Lin, Ji-Fu Lin, Hsien-
Chi Yeh, Pei-li Ho, and Wen-gueyWu Conformational Change and
Inactivation of Membrane Phospholipid-Related Activity of Cardiotoxin
V from Taiwan Cobra Venom at Acidic pH. Biochemistry
, 1996, 35, 9167–9176
109
[58] Chien-Min Chiang; Kun-Yi Chien; Hai-jui Lin; Ji-Fu Lin;
Hsien-Chi Yeh; Pei-li Ho; and Wen-guey Wu. Conformational
Change and Inactivation of Membrane Phospholipid-Related Activity
of Cardiotoxin V from Taiwan Cobra Venom at Acidic
pH.Biochemistry, 1996,35, 9167–9176.
[59] Arun K. Singhal; Kun-Yi Chien; Wen-guey Wu ; and Gordon S
. Rule. Solution Structure of Cardiotoxin V from Naja naja atra.
Biochemistry, 1993, 32, 8036–8044.
[60] Kuschert; G. S. V. ; Coulin, F. ; Power, C. A. ; Proudfoot, A.
E. I. ; Hubbard, R. E. ; Hoogewerf,A. J. ; Wells, T. N. C. .Glycosaminoglycans
Interact Selectively with Chemokines and Modulate
Receptor Binding and Cellular Responses. Biochemistry 1999,
38, 12959–12968.
[61] Hakansson, S. ; Caffrey, M. Structural and Dynamic Properties
of the HIV-1 Tat Transduction Domain in the Free and Heparin-
Bound States. Biochemistry 2003, 42, 8999–9006.
[62] Kumar, R. ; Bose, P. Development and Experimental Validation of
the Model of a Continuous-Flow Countercurrent Ozone Contactor.
Biochemistry 2004, 43, 1418–1429.
[63] Giragossian, C. ; Schaschke, N. ; Moroder, L. ; Mierke, D. F. Conformational
and Molecular Modeling Studies of β-Cyclodextrin-
Heptagastrin and the Third Extracellular Loopof the Cholecystokinin
2 Receptor. Biochemistry 2004, 43, 2724–2731.
[64] Bhunia, Anirban; Jayalakshmi, V. ; Benie, Andrew J. ; Schuster,
Oliver; Kelm, Sorge; Rama Krishna, N. Carbohydra. Res. 2004,
339, 259–267.
[65] Johnson, M. A. ; Jensen, M. T. ; Svensson, B. ; Pinto, B. M.
Selection of a High-Energy Bioactive Conformation of a Sulfonium-
Ion Glycosidase Inhibitor by the Enzyme Glucoamylase G2. J. Am.
Chem. Soc. 2003, 125, 5663–5670.
[66] Francis C. Peterson; E. Sonay Elgin; Timothy J. Nelson; Fuming
Zhang; Theresa J. Hoeger; Robert J. Linhardt; and Brian F. Volkman.
Identification and Characterization of a Glycosaminoglycan
Recognition Element of the C Chemokine Lymphotactin. J. Biol.
Chem. 2004, 279, 12598–12604.
[67] Farhad Forouhar; Wei-Ning Huang; Jyung-Hurng Liu; Kun-Yi
Chien; Wen-guey Wu; and Chwan-Deng Hsiao. Structural Basis
of Membrane-induced Cardiotoxin A3 Oligomerization. J. Biol.
Chem. 2003, 278, 21980–21988. J. Mol. Biol. 1998, 280, 933–52.
[68] Doreleijers, Jurgen F. ; Rullmann, Johan A. C. ; Kaptein, Robert.
Quality Assessment of NMR Structures: A Statistical Survey. J.
Mol. Biol. 1998, 281, 149–164.
110
[69] Scheuermann, Thomas H. ; Lolis, Elias; Hodsdon, Michael E.
Tertiary Structure of Thiopurine Methyltransferase from Pseudomonas
syringae, a Bacterial Orthologue of a Polymorphic, Drug-
Metabolizing Enzyme. J. Mol. Biol. 2003, 333, 573–585.
[70] London, Robert E. Theoretical Analysis of the Inter-Ligand Overhauser
Effect: A New Approach for Mapping Structural Relationships
of Macromolecular Ligands. J. Magn. Reson. 1999, 141, 301–
311.
[71] Dixon, Ann M. ; Widmalm, Goran; Bull, T. E. Modified GOESY
in the Analysis of Disaccharide Conformation. J. Magn. Reson.
2000, 147, 266–272.
[72] Guido Serini; Donatella Valdembri; Sara Zanivan; GiuliaMorterra;
Constanze Burkhardt;Francesca Caccavari; Luca Zammataro;
Luca Primo; Luca Tamagnone; Malcolm Logan; Marc Tessier-
Lavigne;Masahiko Taniguchi; Andreas W. Pchel; Federico Bussolino.
Class 3 Semaphorins Control Vascular Morphogenesis by
Inhibiting Integrin Function. Nature 2003, 424, 391–397.
[73] Kevin Pethe; Sylvie Alonso; Franck Biet; Giovanni Delogu;
Michael J. Brennan; Camille Locht; Franco D. Menozzi. The
Heparin-Binding Haemagglutinin of M. Tuberculosis Is Required
for Extrapulmonary Dissemination. Nature 2001, 412, 190–194.
[74] Federica Castellani; Barth van Rossum; Annette Diehl; Mario
Schubert; Kristina Rehbein; Hartmut Oschkinat. Structure of A
Protein Determined by Solid-State Magic-Angle-Spinning NMR
Spectroscopy. Nature 2002, 420, 98–102.
[75] David G. Morris; Xiaozhu Huang; Naftali Kaminski; Yanli Wang;
Steven D. Shapiro; Gregory Dolganov;Adam Glick; Dean Sheppard.
Loss of Integrin αvβ6-Mediated TGF-β Activation Causes
Mmp12-Dependent Emphysema. Nature 2003, 422, 169–173.
[76] Mario Halic; Thomas Becker; Martin R. Pool; Christian M. T.
Spahn; Robert A. Grassucci; Joachim Frank; Roland Beckmann.
Structure of the Signal Recognition Particle Interacting with the
Elongation-Arrested Ribosome. Nature 2004, 427, 808–814.
[77] Robert Langer; David A. Tirrell. Designing Materials for Biology
and Medicine. Nature 2004, 428, 487–492.
[78] Jamie Rossjohn; Roberto Cappai; Susanne C. Feil; Anna Henry;
William J. McKinstry;Denise Galatis; Lars Hesse; Gerd Multhaup;
Konrad Beyreuther; Colin L. Masters; Michael W. Parker. Crystal
Structure of the N-terminal, Growth Factor-Like Domain of
Alzheimer Amyloid Precursor Protein. Nature Structural Biology
1999, 6, 327–331.
111
[79] JianFeng Chen; Azucena Salas; Timothy A Springer. Bistable Regulation
of Integrin Adhesiveness by Bipolar Metal Ion Cluster. Nature
Structural Biology 2003, 10, 995–1001.
[80] Natalia Beglova; Stephen C. Blacklow; Junichi Takagi; Timothy
A. Springer. Cysteine-Rich Module Structure Reveals a Fulcrum
for Integrin Rearrangement upon Activation. Nature Structural
Biology 2003, 9, 282–287.
[81] Wei-Lien Chuang; Marie Dvorak Christ; and Dallas L. Rabenstein.
Determination of the Primary Structures of Heparin- and
Heparan Sulfate-Derived Oligosaccharides Using Band-Selective
Homonuclear-Decoupled Two-Dimensional 1H NMR Experiments.
Anal. Chem. 2001, 73, 2310–2316
[82] Jonathan A. Lukin and Chien Ho. The Structure-Function Relationship
of Hemoglobin in Solution at Atomic Resolution. Chem.
Rev. 2004, 104, 1219–1230.
[83] Katsuhiko Minoura; Tian-Ming Yao; Koji Tomoo; Miho Sumida;
Masahiro Sasaki; Taizo Taniguchi; and Toshimasa Ishida. Different
Associational and Conformational Behaviors between the Second
and Third Repeat Fragments in the Tau Microtubule-Binding Domain.
Eur. J. Biochem. 2004, 271, 545–552.
[84] Maurizio Pellecchia. ; David Meininger; Qing Dong; Edcon Chang;
Rick Jack & Daniel S. Sem. NMR-Based Structural Characterization
of Large Protein-Ligand Interactions. Journal of Biomolecular
NMR, 2002, 22, 165–173.
[85] Jong W. Yu; Jeannine M. Mendrola; Anjon Audhya; Shaneen
Singh; David Keleti; Daryll B. DeWald; Diana Murray; Scott D.
Emr; and Mark A. Lemmon. Genome-Wide Analysis of Membrane
Targeting by S. cerevisiae Pleckstrin Homology Domains. Molecular
Cell, 2004, 14, 677–688,.
[86] Peter G¨untert. Automatic NMR Structure Calculation. NMR
Workshop, 2004 in Academia Sinica, Taiwan ,powerpoint to pdf
file.
[87] Chi-Fon Chang. Overview of Facility Software for BiomolecularNMR.
NMR Workshop, 2004 in Academia Sinica, Taiwan ,powerpoint
to pdf file.
[88] Christian Blouin; Davin Butt; Andrew James Roger. Rapid Evolution
in Conformational Space: A Study of Loop Regions in A
Ubiquitous GTP Binding Domain. Protein Science, 2004, 13, 608–
616.
[89] Suzanne B. Shuker; Philip J. Hajduk; Robert P. Meadows; Stephen
W. Fesik. Discovering High-Affinity Ligands for Proteins: SAR by
NMR. Science, 274, 1531–1534.
112
[90] Luigi Calzolai; Dominikus A. Lysek; Peter G¨untert; Christine von
Schroetter; Roland Riek; Ralph Zahn; and Kurt W¨uthrich. NMR
Structures of Three Single-Residue Variants of the Human Prion
Protein. Proc. Natl. Acad. Sci. , 2000, 97, 8340–8345.
[91] Lixin Ma; Christopher T. Jones; Teresa D. Groesch; Richard J.
Kuhn; and Carol Beth Post. Solution Structure of Dengue Virus
Capsid Protein Reveals Another Fold. Proc. Natl. Acad. Sci. , 2004,
101, 3414–3419.
[92] S´ebastien J. F. Vincent; Catherine Zwahlen; Carol Beth Post;
John W. Burgner; and Geoffrey Bodenhausen. The Conformation
of NAD+ Bound to Lactate Dehydrogenase Determined by
Nuclear Magnetic Resonance with Suppression of Spin Diffusion.
Proc. Natl. Acad. Sci. , 1997, 94, 4383–4388.
[93] Robert McDermott;; Andreas H. Trabesinger; Michael M¨uck; Erwin
L. Hahn; Alexander Pines; John Clarke. Liquid-State NMR
and Scalar Couplings in Microtesla Magnetic Fields. Science, 2002,
295, 2247–2249.
[94] John Cavanagh et al. “Protein NMR Spectroscopy” Published by
Academic Press. Available at NTHU Library.
[95] Kurt W¨uthrich. “NMR of Proteins and Nucleic Acids” Published
by Wiley-Interscience. Available at NTHU Library.
[96] Ray Freeman. “A Handbook of Nuclear Magnetic Resonance” 2nd
Edition. Published by Longman. Available at NTHU Library.
[97] Peter G¨untert et al. “Workshop oh High Troughput NMR Structure
Determination of Proteins in the Post-Genomic Era” Workshop
data & files. Available at IBMS of Academia Sinica, Taiwan.
[98] Chien-Min Chiang; Shou-Lin Chang; Hai-jui Lin; and Wen-guey
Wu.The Role of Acidic Amino Acid Residues in the Structural
Stability of Snake Cardiotoxins.Biochemistry, 1996, 35, 9177–9186.
[99] Shih-Che Sue; P. K. Rajan; Ting-Shou Chen; Chang-Huain Hsieh;
and Wen-guey Wu. Action of Taiwan Cobra Cardiotoxin on Membranes:
Binding Modes of a β-Sheet Polypeptide with Phosphatidylcholine
Bilayers. Biochemistry, 1997, 36, 9826–9836.
[100] Kavita A. Vyas; Himatkumar V. Patel; Alka A. Vyas; and Wenguey
Wu. Glycosaminoglycans Bind to Homologous Cardiotoxins
with Different Specificity. Biochemistry, 1998, 37, 4527–4534.
[101] Shih-Che Sue; Harold C. Jarrell; Jean-Robert Brisson; and Wenguey
Wu. Dynamic Characterization of the Water Binding Loop
in the P-Type Cardiotoxin: Implication for the Role of the Bound
Water Molecule. Biochemistry, 2001, 40, 12782–12794.
113
[102] Chung-Chuan Lo; Jui-Hung Hsu; You-Cheng Sheu; Chein-Min
Chiang; Wen-guey Wu; Wunshain Fann; and Pei-Hsi Tsao. Effect
of D57N Mutation on Membrane Activity and Molecular Unfolding
of Cobra Cardiotoxin. Biophysical Journal, 1998, 75, 2382–2388.
[103] Yi-Hung Lin; Shao-Chen Lee; Payne Y. Chang; P. K. Rajan; Shih-
Che Sue; Wen-guey Wu. Heparin Binding to Cobra Basic Phospholipase
A2 Depends on Heparin Chain Length and Amino Acid
Specificity. FEBS Letters, 1999, 453, 395–399.
[104] Kun-Yi Chien; Wai-Ning Huang; Jau-Hua Jean; and Wen-guey
Wu. Fusion of Sphingomyelin Vesicles Induced by Proteins from
Taiwan Cobra (Naja naja atra) Venom. J. Biol. Chem. , 1991,
266, 3252–3259.
[105] Kun-Yi Chien; Chien-Min Chian; You-Cheng Hseu; Alka A. Vyas;
Gordon S . Rule; and Wen-guey Wu.Two Distinct Types of Cardiotoxin
as Revealed by the Structure and Activity Relationship
of Their Interaction with Zwitterionic Phospholipid Dispersions.
J. Biol. Chem. , 1994, 269, 14473–14483.
[106] Alka A. Vyas; Jiann-Jong Pan; Himatkumar V. Patel; Kavita A.
Vyas; Chien-Min Chiang; You-Cheng Sheu; Jenn-Kang Hwang;
and Wen-guey Wu. Analysis of Binding of Cobra Cardiotoxins to
Heparin Reveals a New b-Sheet Heparin-binding Structural Motif.
J. Biol. Chem. , 1997, 272, 9661–9670.
[107] Shih-Che Sue; Kun-Yi Chien; Wei-Ning Huang; Joseph K. Abraham;
Kuan-Ming Chen; and Wen-guey Wu. Heparin Binding Stabilizes
the Membrane-bound Form of Cobra Cardiotoxin. J. Biol.
Chem. , 2002, 277, 2666–2673.