請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/75387
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Ting Chen | en |
dc.contributor.author | 陳婷 | zh_TW |
dc.date.accessioned | 2021-07-01T08:12:57Z | - |
dc.date.available | 2021-07-01T08:12:57Z | - |
dc.date.issued | 2003 | |
dc.identifier.citation | 1. Tu, A. T. (1977) Venoms: Chemistry and molecular biology. John Wiley and Sons, New York. 2. Dufton, M. J., and Hider, R. C. (1991) in Snake toxins (Harvey, A. L., Ed., Pergamon Press., Ed.) pp 259-298. New York. 3. Harvey, A. L. Cardiotoxins from snake venoms. (1991) in Handbook of Natural toxins Tu, A. T., Ed., Marcel Dekker, New York, Vol 5, 85-106. 4. Dufton, M. J., and Hider, R. C. (1983) Conformation properties of the neurotoxins and cytotoxins isolated from Elapid snake toxin. CRC Crit. Rev. Biochem. 14, 113-171. 5. Yu, C., Bhaskaran, R., and Yang, C. C. (1994) Structures in solution of toxins from Taiwan cobra, Naja naja atra, derived from NMR spectra. J. Toxin. Toxicol. Rev. 13, 291-315. 6. Dufton, M. J., and Hider, R. C. (1988) Structure and pharmacology of Elapid cytotoxins. Pharmacol. Ther. 36, 1-40. 7. Harvey, A. L. (1985) Cardiotoxins from cobra venoms: possible mechanisms of action. Toxicol. Toxin. Rev. 4, 41-69. 8. Basus, V. J., Song, G., and Hawrot, E. (1993) NMR solution structure of an Ot-bungarotoxin/nicotinic peptide complex. Biochemistry 32, 12290-12298. 9. Conti-Tronconi, B. M., Tang, F., Diethelm, B. M., Wu, X., Tang, F., Beratazzon, T., Schroder, B., Rein-hardt-Maeclicke, S., and Maelicke. (1991) Alpha-bungarotoxin and the competing antibody WF6 interact with different amino acids within the same cholinergic subsi. Biochemistry 30, 2575-2584. 10. Traztos, S. J., and Remoundos, M. S. (1990) Fine localization of the major alpha-bungarotoxin binding-site to residues- a 189-195 of the torpedo acetylcholine receptor residues-189, residues-190, and residues-195, are indispensable for binding. J. Biol. Chem. 265, 21462-21467. 11.Radding, W., Corfield, P. W. R., Levinson, L. S., Hashim, G. A., and Low, B. W. (1988) Alpha-toxin binding to acetyleholine receptor 179-191 peptides-Intrinsic fluorescence studies. FEBS Lett. 231, 212-216. 12.Grognet, J. M., Menez, A., Drake, A., Hayashi, K., Morrison, I. E. G., and Hider, R. C. (1998) Circular dichroic spectra of Elapid cardiotoxins. Eur. J. Biochem. 172, 383-388. 13.Bougis, P. E., Khelifand, A., and Rochat, H. (1989) On the inhibition of [Na+, K+]-ATPases by the components of Naja mossambica mossambica venom: evidence for two distinct rat brain [Na+, K+]-ATPase activities. Biochemistry 28, 3037-3043. 14.Kini, R. M., and Evans, H. J. (1988) Mechanism of platelet effects of cardiotoxins from Naja nigricollis crawshawil (spitting cobra) snake venom. Thromb. Res. 52, 185-195. 15.Hinman, C. L., Lepisco, E., Stevens, R., Mongomery, I. N., Ranch, H. C., and Hudson, R. A. (1987) Effects of cardiotoxin D from Naja Siamensis snake venom upon murine splenic lymphocyt. Toxicon 25, 1011-1014. 16.Takechi, M., Tanaka, Y., and Hayashi, K. (1986) Binding of cardiotoxin analogue Ⅲ from Formosan cobra to FL cells Le. FEBS Lett. 205, 143-146. 17.Gatineau, E., Takeshi, M., Bowet, F., Mansuelle, P., Rochat, H., Harvey, A. L., Montenay-Garestier, T., and Menez. (1990) Delineation of the functional site of a snake venom cardiotoxin: preparation, structure, and function of monoacetylated derivativ. Biochemistry 29, 6480-6489. 18.Vincent, J. P., Balema, M. and Lazdunski, M. (1978) Properties of association of cardiotoxin with lipid vesicles and natural membranes: a case study. FEBS Lett. 85, 103-108. 19.Defourcq, J., and Faucon, J. F. (1978) Specific binding of a cardiotoxjn from Naja mossambica mossambica to charged phospholipids detected by intrinsic fluorescence. Biochemistry 17, 1170-1176. 20.Batenby, A. M., Bougis, P. E., Rochat, H., Verkleij, A. J., and Kruijff, B. (1985) Penetration of a cardiotoxin into cardiolipin model membranes and its implications on lipid organization. Biochemistry 24, 7101-7110. 21.Defourcq, J., Faucon, J. F., Bernard, E., Pezolot, M., Tessier, M., Bougis, P., Rietschoten, J., Delori, P., and Rochat, H. (1982) Structure-function relationships for the cardiotoxins interacting with phospholipids. Toxicon 20, 165-174. 22.O’Connell, J. F., Bougis, P. E., and Wuthrich, K. (1993) Determination of the NMR solution structure of cardiotoxin CTX?(IIb) from Naja mossambica mossambica. Ear. J. Biochem. 213, 891-900. 23.Gilquin, B., Roumestand, C., Zinn-Justin, S., Menez, A., and Toma, F. (1993) Refined three-dimensional solution structure of snake cardiotoxin: analysis of the side-chain organization suggests the existence of a possible phospholipid binding site. Biopolymers 33, 1659-1675. 24.Bhaskaran, R., Huang, C. C., Chang, D. K., and Yu. C. (1994) Cardiotoxin Ⅲ from the Taiwan cobra (Naja naja atra): Determination of structure in solution and comparison with short neurotoxins. J. Mol. Biol. 235, 1291-1301. 25.Jahnke, W., Mier, D. F., Beress, J., and Kesseler, F. I. (1994) Structure of cobra cardiotoxin, CTX I, as derived from Nuclear Magnetic Resonance Spectroscopy and Distance geometry calculation. J. Mol. Biol. 240, 445-458. 26.Bhaskaran, R., Huang, C. C., Tsai, T. C., Jayaraman, G., Chang, D. K., and Yu. C. (1994) Cardiotoxin Ⅱ from Taiwan cobra venom, Naja naja atra. Structure in solution and comparison among homologous cardiotoxins. J. Biol. Chem. 269, 23500-23508. 27.Bilwes, A., Rees, B., Moras, D., Menez, R., and Menez, A. (1994) X-ray structure at 1.55 ? of toxin gamma, a cardiotoxin from Naja nigricollis venom. Crystal packing reveals a model for insertion into membranes. J. Mol. Biol. 239, 122-136. 28.Rees, B., Bilwes, A., Samama, J. P., and Moras, D. (1990) Cardiotoxin?(VII14) from Naja mossambica mossambica: the refined crystal structure. J. Mol. Biol. 214, 281-297. 29.Elliot, R. H. (1905) A contribution to the study of the action of Indian cobra venom Philos. Trans. R. Soc. B197, 361-405. 30.Sharkar, B. B., Maitra, S. R., Ghosh, B. N. (1942) The effect of neurotoxin, haemolysin and choline esterase isolated from cobra venom on heart, blood pressure and respiration. Ind. J. Med. Res. 30, 453-466. 31. Sarker, M. K. (1947) Isolation of cardiotoxin from cobra venom. J. Ind. Chem. Soc. 24, 32.Ravdonat, H. W., and Holler, B. (1958) Ueber die herzwirksame Komponentedes Kobragifies (“Cardiotoxin”). Arch. Exper. Pathol. Pharmakol. 233, 431-437. 33.Kumar, T. K., Jayaraman, G., Lee, C. S., Arunkumar, A. I., Sivaraman, T., Samuel, D., and Yu. C. (1997) Snake venom cardiotoxins-structure, dynamics, function and folding. J Biomol. Struct. Dyn. 15(3), 431-463. 34.Kumar, T. K. S., Lee, C. S., and Yu. C. (1996) A case of cardiotoxin Ⅲ from the Taiwan Cobra. In Natural Toxins, pp. 114-129, Plenum Press, New York. 35.Harvey, A. L. (1991) in Handbook of Natural Toxins, pp 85-106. Marcel Dekker, New York. 36.Yu, C., Bhaskaran, R., Chaung, L. C., and Yang, C. C. (1993) Solution conformation of cobrotoxin: a nuclear magnetic resonance and hybrid distance geometry-dynamical simulated annealing study. Biochemistry, 32, 2131-2136. 37.Tsemoglou, D., Petsko, G. A., McQueen, J. E., and Hermans, J. (1977) Molecular graphics: application to the structure determination of a snake venom neurotoxin. Science 197, 1977-1982. 38.Low, B. W., and Corfield, W. R. (1986) Erabutoxin beta Structure/function relationships following initial protein refinement at 0.140 nm resolution. Eur. J. Biochem. 161(3), 579-587. 39.Roumestand, C., Gilquin, B., Tremeau, O., Gatneau, E., Mouaward, L., Menez, A., and Toma, F. (1994) Proton NMR studies of the structural and dynamical effect of chemical modification of a single aromatic side-chain in a snake cardiotoxin. Relation to the structure of the putative binding site and the cytolytic activity of the toxin. J. Mol. Biol. 243, 719-735. 40.Otting, G., Steinmetz, W. E., Bougis, P. E., Rochat, H., and Wuthrich, K. (1987) Monitoring the purification by high-performance liquid chromatography of cardiotoxins from Naja mossambica mossambica using phase-sensitive two-dimensional nuclear magnetic resonance. Eur. J. Biochem. 168, 609-620. 41.Sun, Y. J., Wu, W.G. Chiang, C. M., Hsin, A. Y., and Hsiao, C. D. (1997) 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 36 (9), 2403-2413. 42.Singhal, A. K., Chien, K. Y., Wu, W. G., and Rule, G. S. (1993) Solution structure of cardiotoxin V from Naja naja atra. Biochemistry 32, 8036-8044. 43.Argos, P., Rossman, M. G., Grau, U. M., Zuber, H., Frank, G., and Iratschin, J. D. (1979) Thermal stability and protein structure. Biochemistry 18, 5698-5703. 44.Adams, M. W. W. (1993) Enzymes and proteins from organisms that grow near and above 100 degrees C. Ann. Rev. Microbiol. 47, 627-658. 45.Alexander, P., Fahnestock, S., Lee, T., Orban, J., and Bryan, P. (1992) Thermodynamic analysis of the folding of the streptococcal protein G IgG-binding domains Bl and B2: why small proteins tend to have high denaturation temperatures. Biochemistry 31(14), 3597-3603. 46.Johnson, C. M., and Fersht, A. R. (1995) Protein stability as a function of denaturant concentration: the thermal stability of barnase in the presence of urea. Biochemistry 34, 6795-6804. 47.Hayashi, K., Takechi, M., Sasaki, T., and Lee, C. Y. (1975) Amino acid sequence of cardiotoxin analogue I from the venom of Naja naja atra. Biochem. Biophys. Res. Commun. 64, 360-366. 48.Kaneda, N., Sasaki, T., and Hayashi, K. (1976) Amino acid sequence of cardiotoxin analogue Ⅱfrom the venom of Naja naja atra. Biochem. Biophys. Res. Commun. 72, 1450-1455. 49.Hayashi, K., Takechi, M., Kaneda, N., and Sasaki, T. (1976) Amino acid sequence of cardiotoxin from the venom of Naja naja atra. FEBS Lett. 66, 210-214. 50.Kaneda, N., Sasaki, T., and Hayashi, K. (1976) The amino acid sequence of cardiotoxin analogue Ⅳ from the venom of Naja naja atra. FEBS Lett. 70, 217-222. 51.Kelly, R. M., Peoples, T. L., Halio, S. B., Rinker, K. D., and Duffaud, G. D. (1994) Extremely thermophilic microorganisms. Metabolic strategies, genetic characteristics, and biotechnological potential. Ann. N. Y. Acad. Sci. 745, 409-425. 52.Hseu, T. H., Jou, E. P., Wang, C., and Yang, C. C. (1977) Molecular evolution of snake venom toxins J. Mol. Evol. 10, 167-182. 53.Dufton, M. J., and Hider, R. C. (1977) Snake toxin secondary structure predictions. Structure activity relationships. J. Mol. Biol. 115,177-193. 54.Hodges, S. J., Agbaji, A. S., Harvey, A. L., and Hider, R. D. (1987) Cobra cardiotoxins. Purification, effects on skeletal muscle and structure/activity relationships. Eur. J. Biochem. 165, 373-383. 55.Lauterwein, J., Lazdweski, M., and Wuthrich, K. (1978) The 1H nuclear-magnetic-resonance spectra of neurotoxin I and cardiotoxin Vii4 from Naja mossambica mossambica. Eur. J. Biochem. 92 (2), 361-371. 56.Mezez, A., Gatineau, E., Roumestand, C., Harvey, A. L., Mauward, L., Gilquin, B., and Toma, F. (1990) Do cardiotoxins possess a functional site Structural and chemical modification studies reveal the functional site of the cardiotoxin from Naja nigricollis. Biochemistry 72, 575-588. 57.Shashidaran, P., and Ramachandran, L. K. (1984) Stabilisation of bacterial protoplasts by cardiotoxin Ⅱ. Ind. J. Biochem. Biophys. 21, 304-308. 58. Srinivasa, B. R., Achyuthan, K. E., and Ramachandran, L. K. (1982) Partial characterization of four toxins from venom of the Indian cobra (Naja naja). Ind. J. Biochem. Biophys. 19, 52-53. 59.Tsetlin, V. I., Arseniev, A. S., Utkin, Y. N., Gurevich, A. Z., Senyavina, L. B., Bystrov, V. F., Ivanov, V. Y., and Ovchinnikov, Y. A. (1979) Conformational studies of neoritoxin Ⅱ from Naja naja oxiana. Selective N-acylation, circular dichroism and nuclear-magnetic-resonance study of acylation products Eur. J. Biochem. 94, 337-346. 60.Shashidaran, P., and Ramachandran, L. K. (1983) Inhibitory activity of cardiotoxin Ⅱ of the Indian cobra & certain antibiotics on lysis of bacteria promoted by lysozyme. Ind. J. Biochem. Biophys. 20, 132-135. 61.Srinivasa, B. R. (1982) Partial characterization of fourtoxins from venom of the Indian cobra (Naja naja). Ind. J. Biochem. Biophys. 19, 52-57. 62.Desormeaux, A,. Laroche, G., Bougis, P. E., and Pezolot, M. (1992) Characterisation by infrared spectroscopy of the interaction of a cardiotoxin with phosphatidic acid and with binary mixtures of phosphatidic acid and phosphatidyl choline. Biochemistry 31, 12173-12182. 63.Chien, K. Y., Huang, W. N., Jean, J. H., and Wu, W. G. (1991) Fusion of sphingomyelin vesicles induced by proteins from Taiwan cobra (Naja naja atra) venom. Interactions of zwitterionic phospholipids with cardiotoxin analogues. J. Biol. Chem. 266, 3252-3259. 64.Condrea, E. (1974) Membrane-active polypeptides from snake venom:cardiotoxins and haemocytotoxins. Experimentia. 30, 121-129. 65.Ksenzhek, O. S., Gevod, V. S., Omeichenko, A. M., Semenov, S. N., Sotnichenko, A. I., and Microschnikov, A. I. (1978) Interaction of cardiotoxin from the venom of the cobra Naja naja oxiana with phospholipid membrane model systems. Molekulyarnaya Biologya. 12,1057-1065. 66.Bougis, P. E., Tessier, M., Rietschoten, J. V., Rochat, H., Faucon, J. F., and Dufourcq, J. (1983) Are interactions with phospholipids responsible for pharmacological activities of cardiotoxins Mol. Cell, Biochem. 55, 49-64. 67.Bougis, P. E., Rochat, H., Pieroni, G., and Verger, R. (1981) Penetration of phospholipid monolayers by cardiotoxins. Biochemistry 20, 4915-4920. 68.Bougis, P. E., Marchot, P., and Rochat, H. (1986) Characterization of elapidae snake venom components using optimized reverse-phase high-performance liquid chromatographic conditions and screening assays for alpha-neurotoxin and phospholipase A2 activities. Biochemistry 25, 723 5-7243. 69.Bougis, P. E., Tiessie, J., Rochat, H., Pieroni, G., Verger, R. (1987) Mixed phospholipid-cardiotoxin monomolecular films studied by intrinsic polarized surface fluorescence. Biochem. Biophys Res. Commun. 143, 506-511. 70.Dufourcq, J., and Faucon, J. F. (1978) Specific binding of a cardiotoxin from Naja mossambica mossambica to charged phospholipids detected by intrinsic fluorescence. Biochemistry 17,1170-1176. 71 .Dufourcq, J., Faucon, J. F., Bernard, E., Pezolet, M., Tessier, M., Bougis, P., Rietschotenm, J. V., Delori, P. and Rochat, H. (1982) Structure-function relationships for cardiotoxins interacting with phospholipids. Toxin 20, 165-174. 72.Batenburg, A. M., Bougis, P. E., Rochat, H., Verkleij, A. J., and Kruijff, B. (1985) Penetration of a cardiotoxin into cardiolipin model membranes and its implications on lipid organization. Biochemistry 24(25), 7101-7110. 73.Hsia, J. C., Er, S. S., and Lee, C. Y. (1978) Effects of Ca2+ and membrane surface charge on the direct lytic activity of cobra cardiotoxin - a membrane spin assay. Biochem. Biophys. Res. Commun.80, 472-476. 74.Condrea, E., Barzilay, M., and Vries, A. D. (1971) Action of cobra venom lytic factor on sialic acid depleted erythrocytes and ghosts. Naunyu Schmiedebergs Arch. Pharmakol. 268, 458-461. 75.Vogt, W., Petzea, P., Lege, L., Oldings, H. D., and Willie, G., (1970) Synergism between phospholipase A and various peptides and SH-reagents in causing haemolysis. Naunyu Schmiedebergs Arch. Pharmakol. 265, 442-454. 76.Tonsing, L., Potgieter, D. J. J., Louw, A. I., and Visser, L. (1983) The binding of snake venom cardiotoxins to heart cell membranes. Biochim Biophys. Acta. 732, 282-288. 77.Fourie, A. M., Meltzer, S., Berman, M. C., and Louw, A. I. (1983) The effect of cardiotoxin on (Ca2+-Mg2+)-ATPase of the erythrocyte and sarcoplasmic reticulum. Biochem. Int. 6, 581-587. 78.Wolff, J., Salabe, H., Ambrose, M., and Larsen, P. R. (1968) The basic proteins of cobra venom. II. Mechanism of action of cobramine B on thyroid tissue. J. Biol. Chem. 243, 1290-1296. 79.Kaneda, N., Hamaguchi, M., Kojiman, M., Kaneshima, H., and Hayashi, K. (1985) Action of cobra venom cardiotoxin on chick embryonal fibroblasts transformed with a temperature-sensitive mutant of Rous sarcoma virus. FEBS Letts. 192, 313-316. 80.Fox, R. O., and Richards, F. M. (1982) A voltage-gated ion channel model inferred from the crystal structure of alamethicin at 1.5-? resolution. Nature 300, 325-330. 81.Vernon, L. P., and Rogers, A. (1992) Binding properties of Pyrularia thionin and Naja naja kaouthia cardiotoxin to human and animal erythrocytes and to murine P388 cells. Toxicon. 30(7), 711-721. 82.Passow, H. (1986) Molecular aspects of band 3 protein-mediated anion transport across the red blood cell membrane. Rev. Physiol. Biochem. Pharmacol. 103, 61-203. 83.Rivas, E. A., M., L. M., and T., G. K. (1981) Isolation of rhodopsin by the combined action of cardiotoxin and phospholipase A2 on rod outer segment membranes. Biochim. Biophys. Acta. 644, 127-135. 84.Rothman, J. E., and Lenard, J. (1977) Membrane asymmetry Science 195, 743-753. 85.Harvey, A. L. (1983) Effect of phospholipase A on actions of cobra venom cardiotoxins on erythrocytes and skeletal muscle. Toxicol. Toxin. Rev. 4, 41-69. 86.Chap, H. J., Zwaal, R. E. A., and Deenan, L. L. M. V. (1977) Action of highly purified phospholipases on blood platelets. Evidence for an asymmetric distribution of phospholipids in the surface membrane. Biochim. Biophys. Acta. 467, 146-151. 87.Fontaini, R. M., Harris, R. A., and Schroeder, F. (1980) Aminophospholipid asymmetry in murine synaptosomal plasma membrane. J. Neurochem. 34, 269-281. 88.Isrealachvilli, J. N., Mareelja, S., and Horn, R. G. (1980) Physical principles of membrane organization. Quat. Rev. Biophys. 13, 121-129. 89.Balema, M., Fosset, M., Chicheportiche, R., Romey, G., and Lazdunski, M. (1975) Constitution and properties of axonal membranes of crustacean nerves. Biochemistry 14, 5500-5508. 90.Dressler, V., Schwister, K., M., C. W., and Deuticke, C. (1983) Dielectric breakdown of the erythrocyte membrane enhances transbilayer mobility of phospholipids. Biochim. Biophys. Acta. 42, 17-21. 91.Shier, W. T., and DuBourdieu, D. J. (1983) Stimulation of phospholipid hydrolysis and cell death by mercuric chloride: evidence for mercuric ion acting as a calcium-mimetic agent. Biochem Biophys Res Commun. 110(3), 758-765. 92.Vernon, L. P. (1996) in Natural Toxins Ⅱ, [A. T. Tu and B. R. Singh, Eds.], pp279-291, Plenum Press, New York. 93.Chiou, S. H., Raynor, R. L., Zheng, B., Chambers, T. C., and Kuo, J. F. (1993) Cobra venom cardiotoxin (cytotoxin) isoforms and neurotoxin:comparative potency of protein kinase C inhibition and cancer cell cytotoxicity and modes of enzyme inhibition. Biochemistry 32, 2062-2067. 94.Chiou, S. H., Chuang, M. H., Hung, C. C., Huang, H. C., Chen, S. T., Wang, K. T., and Lo. C. L. (1995) Inhibition of protein kinase C by snake venom toxins: comparison of enzyme inhibition, lethality and hemolysis among different cardiotoxin isoforms. Biochem. Mol. Biol. International 35, 1103-1112. 95.Sivaraman, T., Kumar, T. K. S., Jayaraman, G., Hen, C. C., and Yu, C. (1997) Characterization of a partially structured state in an all beta-sheet protein. Biochem. J. 321, 457-464. 96.Kumar, T. K., Jayaraman, G., Lee, C. S., Sivaraman, T., Lin, W. Y., and Yu. C. (1995) Identification of ‘molten globule’-like state in all beta-sheet protein. Biochem. Biophys. Res. Commun. 207(2), 536-543. 97.Hung, C. C., Wu, S. H., and Chiou, S. H. (1993) Sequence characterization of cardiotoxins from Taiwan cobra: isolation of a new soform. Biochem. Mol. Biol. Internat. 31(6), 1031-1040. 98.Lin, S. R., Chang, L. S., Chang, K. L. (2002) Separation and structure-function Studies of Taiwan cobra cardiotoxins. J. Protein Chem. 21(2), 81-86. 99.Gill, S. C., and PH, V. H. (1989) Calculation of protein extinction coefficients from amino acid sequence data. Anal Biochem. 182(2), 319-326. 100.Wu, S. H., Wang, K. T., and Ho, C. L. (1982) Purification and pharmacological characterization of a cardiotoxin-like protein from Formosan banded krait (Bungarus multicinctus) venom. Toxicon 20, 753-764. 101. Sivaraman, T., Kumar, T. K. S., Tu, Y. T., Peng, H. J., and Yu, C.(1999) Structurally homologous toxins isolated from the Taiwan cobra (Naja naja atra) differ significantly in their structural stability. Arch.Biochem. Biophys. 363, 107-115. 102. Kyte, J., and Doolittle, R. F. (1982) A simple method for displaying the hydropathic character of a protein. J. Mol. Biol. 157(1), 105-132. 103. Campbell, I. D., and Dwek, R. A. (1984) Biological Spectroscopy, Benjamin/Cummings. Menlo Park, CA. 104. Otwinowski, Z., and Minor, W. (1997) Methods Enzymol. 276, 307-326. 105. Br?nger, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse-Kunstieve, R. W., Jiang, J. S., Kuszewski, J., Nilges, M., Pannu, N. S., Read, R. J., Rice, L. M., Simonson, T., and Warren, G. L. (1998) Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination Acta Crystallogr. D54, 905-921. 106. Jayaraman, G., Kumar, T. K. S., and Yu. C. (1999) Binding of nucleotide triphosphates to cardiotoxin analogue Ⅱ from the Taiwan cobra venom (Naja naja atra) J. Biol. Chem. 274(1), 17869-17875. 107. Raynor, R. L., Zheng, B., and Kuo, J. F. (1991) Membrane interactions of amphiphilic polypeptides mastoparan, melittin, polymyxin B, and cardiotoxin. Differential inhibition of protein kinase C, Ca2+/calmodulin-dependent protein kinase Ⅱ and synaptosomal membrane Na,K-ATPase, and Na+ pump and differentiation of HL60 cells. J. Biol. Chem. 266, 2753-2758. 108. Chakrabarti, A., Bhattacharya, S., Ray, S., and Bhattacharyya, M. (2001) Binding of a denatured heme protein and ATP to erythroid spectrin. Biochem. Biophys. Res. Commun. 282, 1189-1193. 109. Newton, A. C. (1995) Protein kinase C: structure, function, and | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/75387 | - |
dc.description.abstract | 眼鏡蛇毒液中含有許多不同種類的蛋白,其中最主要的兩類是心臟毒蛋白(CTX)與神經毒蛋白(NTX)。CTX是由幾個高相似度的同功異構物(isoform)所組成,它們皆為鹼性(pH>10)、小分子量(6500?7000道耳吞),且具有四個雙硫鍵緊密相繫。這些蛇毒展現多樣性的生物功能,如紅血球細胞的溶血效應、肌肉細胞的去極化與收縮、防止血小板的凝固以及抑制磷脂蛋白激?(phospholipid protein kinase)與鈉鉀離子三磷酸腺??(Na+-K+-ATPase)的活性。為了進一步研究CTX的結構及其生化行為,我們已完成了使用陽離子交換樹脂層析(cation exchange chromatography)與高效能層析法(reverse-phase HPLC)來純化CTX。從高效能層析管柱沖提出的純化蛋白已經由質譜儀(mass spectrometry)正確地確認每一種同功異構物。 目前研究指出,心臟毒蛋白Ⅱ(CTXⅡ)會與四種三磷酸核?(nucleotide triphosphates)(三磷酸尿?(ATP),三磷酸尿?(UTP),三磷酸鳥?(GTP)與三磷酸胞?(CTP))結合,且這個現象被認為是造成蛋白激?C(PKC)與鈉鉀離子三磷酸腺??(Na+-K+-ATPase)活性抑制的原因。在本論文中,藉由使用酪氨酸螢光光譜(tyrosine fluorescence spectroscopy),我們測定各個CTX isoforms與ATP結合的解離係數(dissociation constants)。此外,我們亦完成CTX抑制PKC活性的實驗。然而,我們發現與ATP結合力較佳的蛇毒對PKC卻沒有較強的抑制力,這結果指出CTX與ATP結合並不是抑制PKC活性的原因。接著進行PKC的實驗,我們進一步證實CTX與磷脂類分子(phosPholipids),如磷脂醯絲氨酸(phosphatidylserine(PS))、二脂醯甘油(diacylglycerol (DAG))及diolein結合會造成PKC的活性被抑制。這種抑制作用主要是因蛇毒與磷脂類分子的結合會間接削弱磷脂類分子與PKC結合的能力。此外,我們亦利用圓偏光二色光譜(circular dichroism),螢光光譜及分子模型軟體(molecular modeling)來探討CTX與PS、diolein的結合情形。根據實驗結果,我們相信CTX與磷脂類分子結合必定在抑制PKC活性的功能上扮演重要角色。最後,我們也完成了CTX Ⅲ的結晶實驗並得到初步的繞射圖譜。未來我們將以γ蛇毒(toxin γ)為模型,並嘗試利用分子取代的方法來決定其結構。 | zh_TW |
dc.description.abstract | Snake venoms from the elapid family such as cobra are a mixture of many different types of proteins, of which cardiotoxins (CTXs) and neurotoxins (NTXs) are the two major toxic components. CTXs consist of several highly homologous isoforms, which are highly basic (pI>10.0), small in size (6.5?7.0 kDa) and very compact with four disulfide bonds in each molecule. These toxins display a wide variety of biological activities, such as hemolysis of red blood cells, depolarization and contraction of muscular cells, prevention of platelet aggregation, and blockage of the enzymatic activities of phospholipid protein kinase and Na+-K+-ATPase. In order to study the structures and, in turn, the biochemical behaviors of CTXs, the purification of CTXs was carried out by cation exchange chromatography coupled with reverse-phase HPLC. The purified fractions eluted from HPLC were further characterized by mass spectrometry for the unambiguous identification of each isoform. Previously, CTX Ⅱ was proposed to bind to all four nucleotide triphosphates (ATP, UTP, GTP, and CTP) and believed to cause the inhibitory effects of enzymatic activities, such as protein kinase C and Na+-K+-ATPase. By using the tyrosine fluorescence spectroscopy, we were able to identify the CTX isoforms binding to ATP with different dissociation constants. In addition, the assays for the inhibition of protein kinase C (PKC) activities with CTXs were re-evaluated. Based on our findings, however, it is found that the toxins with higher affinities towards ATP do not display stronger inhibition for PKC activities, indicating that the suppressed effect on PKC activity by CTXs is not due to binding of CTXs to ATP. Using the PKC assay, we further demonstrated that the CTXs binding to phospholipids, such as phosphatidylserine (PS), diacyiglycerol (DAG) and diolein, could account for the blockade effect of PKC activities. The inhibition effect caused by CTXs is primarily due to the ability of toxins to bind to phospholipids, leading to the reduced availability of these molecules to interact with PKC. Moreover, circular dichroism (CD), fluorescence spectroscopy and molecular modeling were used to study the binding of CTX to PS or diolein. According to our results, we believed that the binding of CTXs to phospholidis plays an important role in the inhibition of PKC activities. Finally, crystallization of CTX Ⅲ isoform has been achieved and the preliminary crystal diffraction data will be presented. The structure determination will be attempted by molecular replacement utilizing the structure of toxin γ as the molecular model for future study. | en |
dc.description.provenance | Made available in DSpace on 2021-07-01T08:12:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2003 | en |
dc.description.tableofcontents | 中文摘要……………………………………………1 Abstract……………………………………………2 Chapter 1: Introduction……………………………………………4 Overview of Snake Venoms and Venom Toxins……………………………………………4 History of Cardiotoxin Studies……………………………………………5 Structure of Cardiotoxins……………………………………………6 General Description of Cardiotoxin Structure……………………………………………6 The Structures of Loop I,Ⅱand Ⅲ in Cardiotoxin……………………………………………7 Target sites for CTXs Action……………………………………………9 Possible Mechanisms of Cell Lysis……………………………………………11 Binding and Penetration Model……………………………………………11 Pore-Formation Model……………………………………………12 Membrane Permeability Model……………………………………………12 Cardiotoxin-Phopholipase Synergism Model……………………………………………13 Objective of This Thesis……………………………………………13 Figures and Tables……………………………………………15 Chapter 2: Purification and Characterization of Venom Toxins from Taiwan Cobra……………21 Materials and Methods……………………………………………21 Cation-exchange chromatography……………………………………………21 Reverse-phase HPLC……………………………………………22 Molecular weight analysis by SDS-PAGE……………………………………………22 Circular Dichroism analysis……………………………………………24 Thermal Stability of the CTX isoforms……………………………………………25 Protein sequence analysis of CTX Ⅲ……………………………………………25 Results and Discussion……………………………………………25 Figures and Tables……………………………………………28 Chapter 3: The Crystallization of CTX Ⅲ……………………………………………39 Materials and Methods……………………………………………39 Materials……………………………………………39 Methods……………………………………………40 Results and Discussion……………………………………………42 Figures and Tables……………………………………………45 Chapter 4: Interactions of CTXs with Nucleotides……………………………………………49 The Binding of CTXs to ATP……………………………………………49 Materials and Methods……………………………………………50 Fluorescence experiments……………………………………………50 Calculation of dissociation constants……………………………………………51 Results and Discussion……………………………………………51 Figures and Tables……………………………………………54 Chapter 5: CTXs Inhibit the Protein Kinase C Activities……………………………………62 Summarize of Protein kinase C……………………………………………62 Materials and Methods……………………………………………63 Components of Promega’s SignaTECT PKC Assay System……………………64 Materials to be supplied……………………………………………64 PKC assay protocol……………………………………………65 Preparation of cardiotoxin isoforms……………………………………………67 Results and Discussion……………………………………………67 Figures and Tables……………………………………………70 Chapter 6: Interactions of CTXs with Phosphatidylserine and Diolein………………………76 Materials and Methods……………………………………………77 Circular Dichroism measurement……………………………………………77 Molecular modeling……………………………………………77 Results and Discussion……………………………………………78 Figures and Tables……………………………………………81 Chapter 7: Conclusions and Prospects……………………………………………88 References……………………………………………90 | |
dc.language.iso | zh-TW | |
dc.title | 台灣眼鏡蛇心臟毒蛋白同功異構物抑制蛋白激?C及其與三磷酸腺?和磷酸醯絲氨酸作用之研究 | zh_TW |
dc.title | Study of Cardiotoxin isoforms from Taiwan cobra: Inhibition of protein kinase C and interaction with ATP and phosphatidylserine. | en |
dc.date.schoolyear | 91-2 | |
dc.description.degree | 碩士 | |
dc.relation.page | 99 | |
dc.rights.note | 未授權 | |
dc.contributor.author-dept | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科學研究所 | zh_TW |
顯示於系所單位: | 生化科學研究所 |
文件中的檔案:
沒有與此文件相關的檔案。
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。