臺灣博碩士論文加值系統

在雞母珠種子中含有兩種主要的親醣蛋白質（lectin）：雞母珠毒蛋白（abrin； ABR）與雞母珠凝集素（abrus agglutinin； AAG）。在動物實驗的研究顯示，雞母珠凝集素的半數致死劑量（LD50）為每公斤5毫克遠較雞母珠毒蛋白的半數致死劑量每公斤20毫克低。分析選殖之全長(full-length)雞母珠凝集素之基因，可得雞母珠凝集素之cDNA其開放性密碼(open reading frame; ORF)為1,641鹼基對(base pairs, bp)組成，可轉譯(translation)出547個胺基酸：20個胺基酸組成的訊息胜月太 (signal peptide)，258個胺基酸組成的A鏈，2個胺基酸組成之A(AAG-A)及B鏈(AAG-B)連接片段(linker)及267個胺基酸組成之B鏈。經與雞母珠毒蛋白a (ABRa)比較，共有77.8 %的相似性(similarity)。A鏈與其他核醣體去活性蛋白質（ribosome-inactivating proteins; RIPs）之胺基酸序列在十三個保留（conserved）胺基酸序列及活性位置(active site)是完全相同的。雞母珠凝集素A鏈其對無細胞(cell free)蛋白質生合成系統抑制活性分析之測定結果，其半數抑制濃度(IC50)為3.5 nM，較雞母珠毒蛋白a之A鏈(reABRa-A)為0.05 nM為弱。以雞母珠毒蛋白a之A鏈為模板進行分子模擬(molecular modeling)，並藉由定位突變(site-directed mutagenesis)的方法把雞母珠凝集素A鏈位於a-螺旋結構H(a-helix H)的第199位置脯胺酸突變為天冬醯胺酸之雞母珠凝集素A鏈突變種(AAG-A P199N)，及雞母珠毒蛋白a之A鏈第200位置的天冬醯胺酸突變為脯胺酸之雞母珠毒蛋白a之A鏈突變種(ABRa-A N200P)。經表現及純化突變蛋白質後，由無細胞蛋白質生合成測定活性其半數抑制濃度(IC50)為0.53 nM及2.3 nM，結果顯示脯胺酸可能導致a-螺旋結構H的彎曲進而影響位於28 S核醣RNA次單元體(subunit)上的目標序列(target sequence)，5''-GpApGpAp-3''，的作用，以致雞母珠凝集素之抑制蛋白質生合成之活性及毒性皆較雞母珠毒蛋白a為低之故。

Abrus agglutinin (AAG), a low-toxicity protein from the plant Abrus precatorius, is less lethal than abrina (ABRa) in mice (LD50, 5 mg/kg vs. 20 μg/kg body weight). The nucleotide sequence analysis of a cDNA clone encoding the full-length AAG showed an open reading frame with 1,641 base pairs, corresponding to 547 amino acid residue preproprotein containing a signal peptide and a linker region (2 amino acid residues) between AAG-A and AAG-B subunits. AAG had high homology to ABRa (77.8 %). The 13 amino acid residues involved in catalytic function, which are highly conserved among ABRs and ricins, were also conserved within AAG-A. The protein synthesis inhibitiory activity of AAG-A (IC50, 3.5 nM) was weaker than that of ABRa-A (0.05 nM). Molecular modeling followed by site-directed mutagenesis showed that IC50 of ABRa-A (N200P) and AGG-A (P199N) was dretemined to be 2.3 nM and 0.53 nM, respectively. It suggested that the Pro199 residue of AAG-A, located in the amphiphilic helix H and corresponding to the Asn200 residue of ABRa-A, can induce bending of helix H. This bending would presumably affect the binding of AAG-A to its target sequence, GpApGpAp, in the tetraloop structure of the 28S rRNA subunit and could be one of the major factors contributing to the relatively weak protein synthesis inhibitory activity and toxicity of AAG.

封面
目錄
一、英文摘要
二、摘要
三、緒諭
四、實驗材料
五、實驗方法
六、實驗結果
七、討論
八、圖表及圖表說明p1
九、參考文獻
十、附錄

參考文獻
1.Fitzgerald, D. (1996) Why toxins! Seminars in Cancer Biology 7 : 87-95
2.Fitzgerald, D., and Pastan, I. (1989) Targeted toxin therapy for the treatment of cancer J. Natl. Cancer Inst. 81 : 1455-1461
3.Gabius, H. J., Walzel, H., Joshi, S. S., Kruip, J., Kojima, S., Gerke, V., Kratzin, H., and Gabius, S. (1992) The immunomodulatory b-galactoside specific lectin from mistletoe: partial sequence analysis, cell and tissue binding, and impact on intracellular biosignalling of monocytic leukemia cells. Anticancer Res. 12 : 669-676
4.Horner, W. E., Helbling, A., and Lehrer, S. B. (1993) Basidiomycete allergens: comparsion of three Ganoderma species. Allergy 48 : 110-116
5.Pastan, I., and Fitzgerald, D. (1991) Recombinant toxins for cancer treatment. Science 254 : 1173-1177
6.Bilge, A., Warner, C. V., and Press, O. W. (1995) Translocation of ricin A-chain into proteoliposome reconstituted from Golgi and endoplasmic reticulum. J. Biol. Chem. 270 : 23720-23725
7.Chow, L. P., Chang, K. H., and Lin, J. Y. (1990) Selective cytotoxic effects of immunotoxin-monoclonal anti-AFP-abrin A chain conjugate on several human hepatoma cell lines. Biochem. Intlel. 22 : 95-102
8.Lin, J. Y., Hsieh, Y. S., and Chu, S. S. (1989) Chimeric protein: abrin B chain trypsin inhibitor conjugate as a new antitumor agent. Biochem. Intlel. 19 : 313-323
9.Wawrzhycake, E. J., Zangemeister-Wittke, V., Wiabel, R., Henry, R. V., Parnell, G. D., Cumber, A. J., Jones, M., and Stahel, R. A. (1992) Molecular and biological properties of an abrin A chain immuntoxin designed for therapy of human small cell lung cancer. Br. J. Cancer 66 : 361-366
10.Kernan, N. A., Byers, V., Scannon, P. J., Mischak, R. P., Brochstein, J., Flomenberg, N., Dupont, B., and O’Reilly, R. J. (1988) Treatment of steroid-resistant acute graft-vs-host disease by in vivo administration of an anti-T-cell ricin A chain immunotoxin. J. Am. Med. Assoc. 259 : 3154-3157
11.Kawata, A., Yoshida, M., Okazaki, M., Yotoka, S., Barcos, M., and Seon, B. K. (1994) Establishment of new SCID and nude mouse models of human B leukemia/lymphoma and effective therapy of the tumors with immunotoxin and monoclonal antibody: Marked difference between the SCID and nude mouse models in the antitumor efficacy of monoclonal antibody. Cancer Res. 54 : 2688-2694
12.Barbieri, L., Battelli, M. G., and Stripe, F. (1993) Ribosome inactivating proteins from plants. Biochim. Biophys. Acta 1154 : 237-282
13.Stirpe, F., Gasperi-Campani, A., Barbieri, L., Falasca, A., Abbon-danza, A., and Stevens, W. A. (1983) Ribosome-inactivating proteins from the seeds of Saponaria officinalis L. (soapwort), of Agrostemma githago L. (corn cockle) and of Asparagus officinalis L. (asparagus), and from the latex of Hura crepitans L. (sandbox tree). Biochem. J. 216 : 617-625
14.Stripe, F. S., and Barbieri, L. (1986) Ribosome-inactivating proteins up to date. FEBS Lett. 195 : 1-8
15.Gasperi-Campani, A., Barbieri, L., Battelli, M. G., and Stirpe, F. (1985) On the distribution of ribosome-inactivating proteins among plants. J. Natl. Prod. 48 : 446-454
16.Stirpe, F., Barbieri, L., Battelli, M. G., Soria, M., and Lappi, D. A. (1992) Ribosome-inactivating proteins from plants: present status and future prospects. Bio/Technology 10 : 405-412
17.Robers, W. K., and Selitrennikoff, C. P. (1986) Plant proteins that inactivate foreign ribosomes. Biosci. Reports 6 : 19-29
18.Agnes, D. M., Larergne, J. P., Guillot, D., Sontag, B. L., and Reboud, J. P. (1994) Interaction of phosphorylated elongation factor EF-2 with nucleotides and ribosomes. FEBS Lett. 356 : 283-286
19.van Ness, B. G., Howard, J. B., and Bodley, J. W. (1980) ADP-ribosylation of elongation factor-2 by diphtheria toxin. NMR spectra and proposed structures of ribosyl-diphthamide and its hydrolysis products. J. Biol. Chem. 255 : 10710-10716
20.Endo, Y., Mitsui, K., Motizuki, M., and Tsurug, K. (1987) The mechanism of action of ricin and related toxic lectins of eukaryotic ribosome. J. Biol. Chem. 262 : 5908-5912
21.Canasco, L., Fernandez-Puentes, C., and Vazquez, D. (1975) Effects of ricin on the ribosomal sites involved in the interaction of the elongation factors. Eur. J. Biochem. 54 : 499-503
22.Ready, M. P., Adams, R. P., and Robertus, J. D. (1984) Dodecandrin, a new ribosome-inhibiting protein from Phytolacca dodecandra. Biochim. Biophys. Acta 791 : 314-319
23.Ready, M. P., Wilson, K., Piatak, M., and Robrtus, J. D. (1984) Ricin-like plant toxins are evolutionarily related to single-chain ribosome-inhibiting proteins from phytolacca. J. Biol. Chem. 259 : 15252-15256
24.Robrtus, J. D., and Ready, M. P. (1984) Ricin B chain and discoidin I share a common primitive protein fold. J. Biol. Chem. 259 : 13953-13956
25.Benson, S., Olsnes, S., Pihl, A., Skorue, J., and Abraham, K. A. (1975) On the mechanism of protein-synthesis inhibition by abrin and ricin. Eur. J. Biochem. 59 : 573-580
26.Montanaro, L., Sperti, S., Mattioli, A., Testoni, G., and Stripe, F. (1975) Inhibiton by ricin of protein synthesis in vitro. Biochem. J. 146 : 127-131
27.Nolan, R. D., Grasmuk, H., and Dyews, J. (1976) The binding of tritiated elongation-factors 1 and 2 to ribosomes from krebs II mouse ascites-tumor cells. Eur. J. Biochem. 64 : 69-76
28.Fernandez-Puentes, C., Benson, S., Olsnes, S., and Pihl, A. (1976) Protective effect of elongation factor 2 on the inactivation of ribosomes by the toxic lectins abrin and ricin. Eur. J. Biochem. 64 : 437-443
29.Brigote, M., Carnicelli, D., Alvergna, P., Pallanca, A., Lorenzetti, R., Denaro, M., Speriti, S., and Montanaro, L. (1995) 3’-Immature tRNATrp is required for ribosome inactivation by gelonin, a plant RNA N-glycosidase. Biochem J. 310 : 249-253
30.Veldman, G. M., Klootwijk, J., de Regt, V. C. H. F., Planta, R. J., Branlornt, C., Krol, A., and Ebel, J. P.(1981) The primary and secondary structure of yeast 26 S RNA. Nucleic Acids Res. 9 : 6935-6952
31.Endo, Y., and Wool, I. G. (1982) The site of action of a-sarcin on eukaryotic ribosomes. J. Biol. Chem. 257 : 9054-9060
32.Georgiev, O. I., Nikolaev, N., Hadjiolov, A. A., Skryabin, K. G., Zakharyev, V. M., and Bayer, A. A. (1981) The structure of the yeast ribosomal RNA gene: complete sequence of the 25 S rRNA gene from Saccharomyces cerevisiae. Nucleic Acids Res. 9 : 6953-6958
33.Brosius, J., Dull, T. J., and Voler, H. F. (1980) Complete nucleotide sequence of a 23 S ribosomal RNA gene from Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 77 : 201-204
34.Heus, H. A., and Pardi, A. (1991) Structural features that give rise to the unusual stability of RNA hairpins containing GNRA loops. Science 253 : 191-194
35.Gluck, A., Endo, Y., and Wool, I. G. (1992) Ribosomal RNA identity elements for ricin A-chain recognition and catalysis. J. Mol. Biol. 226 : 411-424
36.Endo, Y., Huber, P. W., and Wool, I. G. (1983) The ribonuclease activity of the cytotoxin a-sarcin. J. Biol. Chem. 258 : 2662-2667
37.Vater, C. A., Bartle, L. M., Leszyk, J. D., Lambert, J. M., and Goldmacher, V. S. (1995) Ricin A chain can be chemical cross-linked to mammalian ribosomal proteins L9 and L10e. J. Biol. Chem. 270 : 12933-12940
38.Hudak, K. A., Dinman, J. D., and Tumer, N, E. (1999) Pokeweed antiviral protein accesses ribosomes by binding to L3. J. Biol. Chem. 274 : 3859-3864
39.Brigotte, M., Carnicelli, D., Alvergna, P., Pallanca, A., Sperti, S., and Montanaro, L. (1995) Differential up-regulate by tRNAs of ribosome-inactivating proteins. FEBS Lett. 373 : 115-118
40.Barbieri, L., and Stripe, F. (1982) Ribosome-inactivating proteins from plants: properties and possible uses. Cancer Surveys 1 : 489-520
41.Olsnes, S., and Phil, A. (1973) Different biological properties of the two constituent peptide chains of ricin, a toxic protein inhibiting protein synthesis. Biochemistry 12 : 3121-3126
42.Halling, K. C., Halling, A. C., Murray, E. E., Ladin, B. F., Houston, L. L., and Weaver, R. F. (1985) Genomic cloning and characterization of a ricin gene from Ricinus communis. Nucleic Acids Res. 13 : 8019-8033
43.Lin, J. Y., Shaw, Y. S., and Tung, T. C. (1971) Studies on the active principle from Abrus precatorius L. Leguminoxal seeds kernels. Toxicon. 9 : 97-101
44.Gasperi-Campani, A., Barbieri, L., Lorenzoni, E., Montanaro, L., Sperti, S., Bonetti, E., and Stripe, F. (1978) Modeccin, the toxin of Adenia digitata: purification, toxicity and inhibition of protein synthesis in vitro. Biochem. J. 174 : 491-496
45.Stripe, F., Legg, R. F., Onyon, L. J., Ziska, P., and Franz, H. (1980) Inhibition of protein synthesis by a toxic lectin from Viscum album L. (mictletoe). Biochem. J. 190 : 843-845
46.Makela, O. (1957) Blood group A of human. Ann. Med. Exp. Biol. Fenn. 35 : 11-33
47.Marinkovich, V. (1964) Purification and characterization of the hemagglutinin present in potatoes. J. Immunol. 93 : 732-738
48.Boyd, W., and Brown, R. (1965) A specific agglutinin in the snail, Octala lactea. Nature 280 : 584-593
49.Hammeratorm, S., and Kabat, E. (1969) Purification and characterization of a blood group A reactive hemagglutinin from the snail, Helix pomatia, and a study of its combining site. Biochemistry 8 : 2696-2705
50.Cushing, J. (1953) Individual variation in the hemagglutinin content of Yellowfin tuna and bloods skipjack. J. immunol. 68 : 543-544
51.Johnson, H. (1964) Human blood group A specific agglutinin of butter clam, Saxidomus gigantens. Science 146 : 548-549
52.Berheimer, A. (1952) Hemagglutinin in caterpillar bloods. Science 115 : 150-152
53.Stockert, T., Morell, A., and Schernberg, I. (1974) Mammalian hepatic lectin. Science 186 : 365-366
54.Hydgin, R., Pricer, W., Ashwell, G., and Stockat, R. (1974) The isolation and properties of a rabbit liver binding protein specific for asilo-glycoproteins. J. Bilol. Chem. 249 : 5536-5543
55.Olsnes, S., Rofsnes, K., Christensen, T. B., and Pihl, A. (1975) Studies on the structures and properties of the lectins from Abrus precatorius and Ricinus communis. Biochim. Biophys. Acta 405 : 1-10
56.Draper, R. K., and Simon, M. I. (1980) The entry of diphtheria toxin into the mammalian cell cytoplasm: evidence of lysosomal involvement. J. Cell Biol. 87 : 849-854
57.Sandvig, K., and Olsnes, S. (1981) Rapid entry of nicked diptheria toxin into cells at low pH. Characterization of the entry process and effect of low pH on the toxin molecule. J. Biol. Chem. 256 : 9068-9076
58.Collier, R. J. (1967) Effect of diphtheria toxin on protein synthesis : inactivation of one of the transfer factors. J. Mol. Biol. 25 : 83-98
59.Sandvig, K., Olsnes, S., and Pihl, A. (1976) Kinetics of binding of the toxic lectins abrin and ricin to surface receptors of human cells. J. Biol. Chem. 251 : 3977-3984
60.Chan, L. N. L., Li, J. S., and Liu, S. Y. (1985) Differential effects of abrin on normal and tumor cells. J. Cell Physiol. 123 : 132-138
61.Nicolson, G. L., Lacobiere, M., and Hunter, T. R. (1972) Mechanism of cell entry and toxicity of an affinity- purified lectin from Ricinus communis and its differential effects on normal and virus-transformed fibroblasts. Cancer Res. 35 : 144-155
62.Lendaro, E., Ippoliti, R., Belleli, A., Brunori, M., Evangelista, V., Guidarini, D., and Benedetti, P. A. (1994) Intracellular dynamics of ricin followed by fluorescence microscopy on living cells reveals a rapid accumulation of the dimeric toxin in the Golgi apparatus. FEBS Lett. 344 : 99-104
63.Yoshida, T., Chen, C., Zang, M., and Wu, H. C. (1991) Disruption of Golgi apparatus by brefeldin A inhibits the cytotoxicity of ricin, modeccin and Pseudomonas toxin. Exp. Cell Res. 192 : 389-395
64.Sandvig, K., Prydz, K., Hansen, S. H., and van Deurs, B. (1991) Ricin transport in brefeldin A-treated cells: Correlation between Golgi structure and toxic effect. J. Cell Biol. 115 : 971-981
65.Bilge, A., Warner, C. V., and Press, O. W. (1995) Translocation of ricin A-chain into proteoliposome reconstituted from Golgi and endoplasmic reticulum. J. Biol. Chem. 270 : 23720-23725
66.Lambert, J. M., Goldmacher, V. S., Collinson, A. R., Nadler, L. M., and Blattler, W. A. (1991) An immunotoxin prepared with blocked ricin: A natural plant toxin adapted for therapeutic use. Cancer Res. 51 : 6236-6242
67.Timar, J., McIntosh, D. P., Henry, R., Cumber, A. J., Parnell, G., and Davies, A. J. S. (1991) The effect of ricin B chain on the intracellular trafficking of an A chain immunotoxin. Br. J. Cancer 64 : 655-662
68.Agapov, I. I., Tonevitsky, G., Shamshiev, A. T., Pohl, E., Pohl, P., Palmer, R. A., and Kirpichnikov, M. P. (1997) The role of structural domains in RIP II toxin model membrane binding. FEBS Lett. 402 : 91-93
69.Chaudhary, V. K., Jinno, Y., FitzGearld, D., and Pastan, I. (1990) Pseudomonas exotoxin contains a specific sequence at the carboxyl terminus that is required for cytotoxicity. Proc. Natl. Acad. Sci. U.S.A. 87 : 308-312
70.Peter, F., Van, P. N., and Soling, H. D. (1992) Different sorting of Lys-Asp-Glu-Leu proteins in rat liver. J. Biol. Chem. 267 : 10631-10637
71.Unwin, N., and Henderson, R. (1984) The structure of proteins in biological membranes. Sci Am. 250 : 78-85
72.Lord, J. M., Roberts, L. M., and Robertus, J. D. (1994) Ricin: structures, mode of action and some current applications. FASEB J. 8 : 201-208
73.Walter, P., Gilmore, R., and Blobel, G. (1984) Protein translocation across the endoplasmic reticulum, Cell 38 : 5-16
74.Hughes, J. N., Lindsay, C. D., and Griffths, G. D. (1996) Morphology of ricin and abrin exposed endothelial cells in consistent with apoptotic cell death. Human Exp. Toxicol. 15 : 443-451
75.Sandvig, K., and van Deurs, B. (1992) Toxin-induced cell lysis: protection by 3-methyladenine and cycloheximide. Exp. Cell Res. 200 :253-262
76.Weston, S. A., Tucker, A. D., Thatcher, D. R., Derbyshier, D. J., and Pauptit, R. A. (1994) X-ray structure of recombinant ricin A-chain at 1.88 Å resolution. J. Mol. Biol. 244 : 410-422
77.Chow, T. P., Feldman, R. A., Lovett, M., and Piatak, M. (1990) Isolation and DNA sequence of a gene encoding a-trichosanthin, a type I ribosome-inactivating protein. J. Biol. Chem. 265 : 8670-8674
78.Benatti, L., Saccardo, M. B., Dani, M., Bitti, G. P., Sassano, M., Lorenzetti, R., Lappi, D. A., and Soria, M. (1989) Nucleotide sequence of cDNA doking for saporin-6, a type-I ribosome-inactivating protein from Saponaria officinalis. Eur. J. Biochem. 183 : 465-470
79.Ho, W. K. K., Liu, S. C., Shaw, P. C., Yeung, H. W., Ng, T. B., and Chan, W. Y. (1991) Cloning of the cDNA of a-momorcharin : a ribosome-inactivating protein. Biochim. Biophys. Acta 1088 : 311-314
80.Roberts, L. M., and Lord, J. M. (1981) The synthesis of Ricinus communis agglutinin : cotranslation and posttranslation modification of agglutinin polypeptides. Eur. J. Biochem. 119 : 31-41
81.Lord, J. M. (1985) Synthesis and intracellular transport of lectin and storage protein precursors in endosperm from castor bean. Eur. J. Biochem. 146 : 403-409
82.Lord, J. M. (1985) Precursor of ricin and Ricinus communis agglutinin glycosylation and processing during intracellular transport. Eur. J. Biochem. 146 : 411-416
83.Scott, M. P., Jung, R., Muntz, K., and Nielsen, N. C. (1992) A protease responsible for posttranslational cleavage of a conserved Asn-Gly linkage in glycinin, the major seed storage protein of soybean. Proc. Natl. Acad. Sci. U.S.A. 89 : 658-662
84.Coleman, W. H., and Roberts, W. K. (1982) Inhibitors of animal cell-free protein synthesis from grains. Biochim. Biophys. Acta 696 : 239-244
85.Irvin, J. D. (1975) Purification and partial characterization of the antiviral protein from Phytolacca americana with inhibits eukaryotic protein synthesis. Arch. Biochem. Biophys. 169 : 522-528
86.Tomlinson, J. A., Walker, V. M., Flewett, T. H., and Barclay, G. R. (1974) The inhibition of infection by cucumber mosaic virus and influenza virus by extracts from Phytolacca americana. J. Gen. Virol. 22 : 225-232
87.Barbieri, L., Aron, G. M., Irvin, J. D., and Stripe, F. (1982) Purification and partial characterization of another form of the antiviral protein from the seeds of Phytolacca americana L. (pokeweed). Biochem. J. 203 : 55-59
88.Yamaizumi, M., Uchida, T., and Okada, Y. (1979) Macromolecules can penetrate the host cell membrane during the early period of incubation with HVJ (sendai virus). Virology 95 : 218-221
89.Fernandez-Puentes, C., and Carrasco, L. (1980) Viral infection permeabilizes mammalian cells to protein toxins. Cell 20 : 766-795
90.McGrath, M. S., Huang, K. M., Caldwell, S. E., Gaston, I., Luk, K. C., Wu, P., Ng, V. L., Crowe, S., Daniels, J., Marsh, J., Deinhart, T., Lekas, P. V., Vennari, J. C., Yeung, H. W., and Lifson, J. D. (1989) GLQ233: an inhibitor of human immunodeficiency virus replication in acutely and chronically infected cells of lymphocyte and mononuclear phagocyte lineage. Proc. Natl. Acad. Sci. U.S.A. 86 : 2844-2848
91.Lee-Huang, S., Kun, H. F., Huang, P. L., Li, B. Q., Huang, P., Huang, H. I., and Chen, H. C. (1991) A new class of anti-HIV agents: GAP31, DAPs30 and 32. FEBS Lett. 291 : 139-144
92.Wang, Y. X., Neamati, N., Jacob, J., Kaufman, J. D., Huang, P. L., Huang, P. L., Winslow, H. E., Pommier, Y., Wingfield, P. T., Lee-Huang, P., Bax, A., and Torchia, D. A. (1999) Solution structure of anti-HIV-1 and anti-tumor protein MAP30: structural insights into its multiple functions. Cell 99 : 433-442
93.Yeung, H. W., Li, W. W., Feng, Z., Barbieri, L., and Stirpe, F. (1988) Trichosanthin, a-momorcharin and b-momorcharin : identity of abortifacient and ribosome-inactivating proteins. Intl. J. Pept. Protein. Res. 31 : 265-268
94.Sharon, N. (1977) Lectins. Sci Am. 6 : 108-109
95.Tung, T. C. (1978) Studies on toxic proteins of seeds of Abrus precatorius. J. Formosan. Med. Assoc. 77 : 699-705
96.Auler, H. (1928) Abrin. Periodico aj medicina chirurgia ed Igiene 35 : 310-312
97.Treves, A. J., Cohen, I. R., and Feldman, M. S. (1975) Immunotherapy of lethal metastasis of lymphocytes sensitized against tumor cells in vitro. J. Natl. Cancer Inst. Res. 777-780
98.Ling, K. H., and Tung T. C. (1948) The oxidative demethylation of monomethyl-L-amino-acids. J. Biol. Chem. 174 : 643-645
99.Tung, T. C., Liau, M. C., (1960) Studies on the chemical components of the seed of Abrus precatorius. J. Formasan. Med. Assoc. 59 : 868-875
100.Lin, J. Y., Lei, L. L., and Tung, T. C. (1969) Purification of abrin from Abrus precatorius. L. Leguminosae. J. Formosan. Med. Assoc. 68 : 468-477
101.Lin, J. Y., Tserng, K. Y., Chen, C. C., Lin, L. T., and Tung, T. C. (1970) Abrin and ricin new anti-tumour substances. Nature 227 : 292-293
102.應紹舜 (1987) 台灣高等植物彩色圖誌 Vol.2. pp. 453-455
103.甘偉松 (1981) 藥用植物學pp. 308-309國立中國醫藥研究所出版.
104.Olsnes, S., and Phil, A. (1982). Mechanism of action. In Molecular Action of Toxins and Viruses (Cohen, P. & Van Heyningen, S., eds), pp. 51-105, Elsevier Scientific Publishing Co., New York.
105.Wei, C. H., Koh, C., Pfuderer, P., and Einstein, Jr. (1975) Purification, properties, and crystallinographic data for a principal nontoxic lectin from the seeds of Abrus precatorius. J. Biol. Chem. 250 : 4790-4795
106. Lin, J. Y., Lee, T. C., Hu, S., and Tung, T. C. (1981) Isolation of four isotoxic proteins and one agglutinin from jequiriti bean (Abrus precatorius). Toxicon 19 : 41-51
107.Nicolson, G. L. (1974) Ultrastructural analysis of toxin binding and entry into mammalian cells. Nature 251 : 628-630
108.Wu, A. M., Watkins, W. M., Chen, C. P., Song, S. C., Chow, L. P., and Lin., J. Y. (1995) Native and/or asialo-Tamm-Horsfall glycoproteins Sd(a+) are important receptors for Triticum vulgaris (Wheat germ) agglutinin and for three toxic lectins (abrin-a, ricin and mistoletoe toxic lectin-I.) FEBS Lett. 371 : 32-34
109.Tung, T.C., Chang, H. C., Hsu, Y. M., and Lin, J. Y. (1979) Antigenicity of abrus agglutinin-treated Meth-A tumor cells in inbred Balb/c mice. J. Formosan. Med. Assoc. 78 : 923-933
110.Tung, T. C., Chang, H. C., Hsu, Y. M., Hsu, C. T., and Lin, J. Y. (1979) Tumor immunity induction in inbred Balb/c mice by abrus agglutinin-treated Meth-A fibrosarcoma cells. J. Formosan. Med. Assoc. 78 : 605-607
111.Lin, J. Y., Li, J. S., and Tung, T. C. (1981) Lectin derivatives of methotrexate and chlorambucil as chemotherapeutic agents. J. Natl. Cancer Inst. 66 : 523-528
112.Tung, T. C., Yang, T. T., Chang, H. C., Hsu, Y. M., and Lin, J. Y. (1981) The growth inhibition of S-180 sarcoma cells by abrus agglutinin treatment in vivo. J. Formosan. Med. Assoc. 80 : 1-6
113.丁令白 (1976) 雞母珠凝血蛋白及毒蛋白之研究 國立臺灣大學醫學院生化學研究所六十四學年度碩士論文
114.李德章 (1980) 由雞母珠種子分離及鑑定異毒蛋白與凝集素之研究 國立臺灣大學醫學院生化學研究所六十八學年度博士論文
115.李建雄 (1980) (1)雞母珠毒蛋白及親醣蛋白與Methotrexate, Chlorambucil或Doxorubicin之共價複合物的抗癌研究 (2) 雞母珠毒蛋白之硝化研究 國立臺灣大學醫學院生化學研究所六十八學年度碩士論文
116.Funatsu, G., Taguchi, Y., Kamenosono, M., and Yanaka, M. (1988) The complete amino acid sequence of A-chain of abrin-a, a toxic protein from the seeds of Abrus precatorius. Agric. Biol. Chem. 52 : 1095-1097
117.Chen, Y. L., Chow, L. P., Tsugita, A., and Lin, J. Y. (1992) The complete primary structure of abrin-a B chain. FEBS Lett. 309 : 115-118
118.Hung, C. H., Lec, M. C., Lee, T. C., and Lin, J. Y. (1993) Primary structure of three distinct isoabrins determined by cDNA sequencing. J. Mol. Biol. 229 : 263-267
119.洪志宏 (1993) Part I:由相思樹胰蛋白酶抑制劑基因及其突變種之選殖研究其構造與作用機制之關係 Part II:在基因層次研究異雞母珠之構造及功能 國立臺灣大學醫學院生化學研究所八十一學年度博士論文
120.汪俐穎 (1999) 雞母珠凝集素之胺基酸序列分析 國立臺灣大學理學院動物學系八十七學年度學士論文
121.Rutenber, E., Katzin, B., J.,Ernst, S., Collins, E. J., Mlsna, D., Ready, M. P., and Robertus, J. D. (1991) Crystallographic refinement of ricin to 2.5 Å. Proteins 10 : 240-250
122.Tahirov, T. H., Lu, T. H., Liaw, Y. C., Chen, Y. L., and Lin, J.Y. (1995) Crystal structure of abrin-a at 2.14 Å. J. Mol. Biol. 250 : 354-367
123.Hung, C. H., Lee, M. C., Chen, J. K., and Lin, J. Y. (1994) Cloning and expression of three abrin-a A chains and their mutants derived by site-specific mutagenesis in Escherichia coli. Eur. J. Biochem. 219 : 83-87
124.Funatsu, G., Islam, M. R., Minam, Y., Sung-Sil, K., and Dimura, M. (1991) Conserved amino acid residues in ribosome-inactivating proteins from plants. Biochimie 73 : 1157-1161
125.Yan, X., Hollis, T., Svinth, M., Day, P., Monzingo, A. F., Milne George W. A., and Robertus J. D. (1997) Structure-based identification of ricin inhibitor. J. Mol. Biol. 266 : 1043-1049
126.Monzingo, A. F., and Robertus, J. D. (1992) X-ray analysis of substrate analogs in the ricin A-chain active site. J. Mol. Biol. 227 : 1136-1145
127.Terwilliger, T. C., and Eisenberg, D. (1982) The structure of melittin. Structure determination and partial refinement. J. Biol. Chem. 257 : 6016-6022
128.Uckun, F. M., Haissig, S., Ledbetter, J. A., Fidler, P., Myers, D. E., Kuebelbeck, V., Weisdrof, D., Gajl-Peczalska, K., Kersey, J. H., and Ramsay, N. K. C. (1992) Developmental Hierarchy during early human B cell ontogeny after autologous bone marrow transplantation using autographs depleted of CD19+ B cell precursors by an anti-CD19 Pan-B-cell immunotoxin containing pokeweed antiviral proteins. Blood 79 : 33669-3379
129.Byers, V. S., Rodvien, R., Grant, K., Durrant, L. G., Hudson, K. H., Baldwin, R. W. and Scanon, P. J. (1989) Phase I study of monoclonal antibody-ricin A chain immunotoxin Xomazyme-791 in patients with metastatic colon cancer. Cancer Res. 49 : 6153-6160
130.Weiner, L. M., O’Dwyer, J., Kitson, J., Comis, R. L., Frankel, A. E., Bauer, R. J., Konrad, M. S., and Groves, E. S. (1989) Phase I evaluation of an anti-breast carcinoma monoclonal antibody 260F9-recombinant ricin A chain immunoconjugate. Cancer Res. 49 : 4062-4067
131.Engert, A., Diehl, V., Schnell, R., Radszuhn, A., Hatwig, M. T., Drillich, S., Schon, G., Bohlen, H., Tesch, H., Hansmann, M. L., Barth, S., Schindler, J., Ghetie, V., Uhr, J., and Vitetta, E. (1997) A phase-I study of an anti-CD25 ricin A-chain immunotoxin (RFT5-SMPT-dgA) in patients with refractory Hodgkin’s lymphoma. Blood 89 : 403-410
132.Soler-Rodriguez, A. M., Uhr, J. W., Richardson, J., and Vitetta, E. S. (1992) The toxicity of chemically deglycosylated ricin A-chain in mice. Intl. J. Immunopharmac. 14 : 281-289
133.Soler-Rodriguez, A. M., Ghetie, M. A., Oppenheimer-Marks, N., Uhr, J. W., and Vitetta, E. S. (1993) Ricin A-chain and ricin A-chain immunotoxins rapidly damage human endothelial cells implication for vascular leak syndrome. Exp. Cell Res. 206 : 227-234
134.Griffths, G. D., Lindsay, C. D., and Upshall, D. G. (1994) Examination of the toxicity of several protein toxins of plant origin using bovine pulmonary endothelial cells. Toxicology 90 :11-27
135.Smith, P. K., Krohn, R. I., Hermanson, G. T., Mallia, A. K., Gartner, F. H., Provenzano, M. D., Fujimoto, E. K., Goeke, N. M., Olson, B. J., and Klenk, D. C. (1985) Measurement of protein using bicinchoninic acid. Anal. Biochem. 150 : 76-85
136.Laemmli, U. K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227 : 680-685
137.Schägger, H., and von Jagow, G. (1987) Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal. Biochem. 166 : 368-379
138.Zacharius, R. M., Zell, T. E., Morrison, J. H., and Woodlock, J. J. (1969) Glycoprotein staining following electrophoresis on acrylamide gels. Anal. Biochem. 30 : 148-152
139.Merrill, C.R. (1980) Ultrasensitive stain for proteins I polyacrylamide gels shows regional variation in cerebrospinal fluid proteins. Science 211 : 1437-1438
140.Matasudaira, P. (1987) Sequence from picomole quantities of proteins electroblotted onto polyvinylidene difluoride membrane. J. Biol. Chem. 262 : 10035-10038
141.Ulrich, A., Shine, J., Chrigfwin, J., Pictet, R., Tischer, E., Rutter, W. J., and Goodman, H. M. (1977) Rat insulin genomes: construction of plasmids containing the coding sequence. Science 196 : 1313-1316
142.Sambrook, J., Fritsch, Z. F. and Maniatis, T. (1989) Molecular Cloning : A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York
143.Wu, T. H., Chow, L. P., and Lin, J. Y. (1998) Sechiumin, a ribosome-inactivating protein from the edible gourd, Sechium edule swarts. Eur. J. Biochem. 255 : 400-408
144.Chung, C. T., and Miller R. H. (1989) A rapid and convenient method for the preparation and storage of competent bacterial cells. Proc. Natl. Acad. Sci. U.S.A. 86 : 2172
145.Sanger, F., Nicklen, S., and Coulson, A. R. (1977) DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. Sci. U.S.A. 74 : 543-547
146.Smith, L. M., Sanders, J. Z., Kaiser, R. J., Huges, P., Dodd, C., Connell, C. R., Heiner, C., Kent, S. B. H., and Hood, L. E. (1986) Fluorescence detection in automated DNA sequence analysis. Nature 321 : 674-679
147.Smith, D. B., and Johnson, K. S. (1988) Single-step purification of polypeptide expressed in Escherichia coli as fusions with glutathione S-transferase. Gene 67 : 31-40
148.Jackson, R. J., and Hunt, T. (1983) Preparation and use of nuclease-treated rabbit reticulocyte lysates for the translation of eukaryotic messenger RNA. Methods Enzymol. 96 : 50-74
149.Wettstein, F. O., Staehelin, T., and Noll, H. (1963) Ribosomal aggregate engaged in protein synthesis: characterization of the ergosome. Nature 197 : 430-435
150.Garren, L. D., Richardson, A. P., and Crocco, R. M. (1967) Studies on the role of ribosomes in the regulation of protein synthesis in hypophysectomized and thyroidectomized rats. J. Biol. Chem. 242 : 650-656
151.Sallustio, S., and Stanley, P. (1990) Isolation of Chinese hamster ovary ribosomal mutants differentially resistant to ricin, abrin and modeccin. J. Biol. Chem. 265 : 582-588
152.Calhoun, D. B., Vanderkooi, J. M., and Englander, S. V. (1983) Penetration of small molecules into proteins studied by quenching of phosphorescence and fluorescence. Biochemistry 22 : 1533-1539
153.Eftink, M. R., and Ghiron, C. A. (1981) Fluorescence quenching studies with proteins. Anal. Biochem. 114 : 199-227
154.Peitsch, M. C., Wells, T. N., Stampf, D. R., and Sussman, J. L. (1995) The Swiss-3D Image collection and PDB-Browser on the World-Wide Web. Trends Biochem. Sci. 20 : 82-84
155.Peitsch, M. C. (1996) ProMod and Swiss-Model: Internet-based tools for automated comparative protein modeling. Biochem. Soc. Trans. 24 : 274-279
156.Guex, N., and Peitsch, M. C. (1997) SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18 : 2714-2723
157.Kyte, J., and Doolittle, R. F. (1982) A simple method for displaying the hydropathic character of a protein. J. Mol. Biol. 157 : 105-132
158.Houston, L. L., and Dooley, T. P. (1982) Binding of two molecules of 4-methylumbelliferyl N-acetylgalactosamine to the B chains of ricin and Ricinus communis agglutinin and to purified ricin B-chain. J. Biol. Chem. 257 : 4147-4151
159.Chen, J. K., Hung, C. H., Liaw, Y. C., and Lin, J. Y. (1997) Identification of amino acid residues of abrin-a A chain is essential for catalysis and reassociation with abrin-a B chain by site-directed mutagenesis. Protein Eng. 10 : 827-833
160.陳媛孃 (1993) 雞母珠毒蛋白質(Abrin-a)胺基酸排列順序之研究 國立臺灣大學醫學院生化學研究所八十一學年度博士論文
161.Evensen, G., Mathiesen, A., and Sundan, A. (1991) Direct molecular cloning and expression of two distinct abrin A-chains. J. Biol. Chem. 266 : 6848-6852
162.Wood, K. A., Lork, J. M., Wawrzynczak, E. J., and Piatak, M. (1991) Preproabrin : genomic cloning, characterization and the expression of the A-chain in Escherichia coli. Eur. J. Biochem. 198 : 723-732
163.Hegde, R., and Podder, S. K., (1998) Evolution of tetrameric lectin Ricinus communis agglutinin from two variant groups of ricin toxin dimers. Eur. J. Biochem. 254 : 596-601
164.Morris, K. N., and Wool, I. G. (1994) Analysis of the contribution of an amphiphilic a-helix to the structure and to the function of ricin A chain. Proc. Natl. Acad. Sci. U.S.A. 91 : 7530-7533
165.Shinde, U., and Inouy, E. (1993) Intramolecular chaperones and protein folding. Trends Biochem. Sci. 18: 442-446
166.Morris, K. N., and Wool, I. G. (1992) Determination by systematic deletion of the amino acids essential for catalysis by ricin A chain. Proc. Natl. Acad. Sci. U.S.A. 89 : 4869-4873
167.Kitaoka, Y. (1998) Involvement of the amino acids outside the active-site cleft in the catalysis of ricin A chain. Eur. J. Biochem. 257, 255-262
168.陳錦坤 (1997) 以定位突變法研究雞母珠毒蛋白A鏈之結構與功能 國立臺灣大學醫學院生化學研究所八十六學年度博士論文
169.Kaku, H., Tanaka, Y., Tazaki, K., Minami, E., Mizuno, H., Shibuya, N., (1996) Sialylated oligosaccharide-specific plant lectin from Japanese elderberry (Sambucus sieboldiana) bark tissue has a homologous structure to type II ribosome-inactivating proteins, ricin and abrin. cDNA cloning and molecular modeling study. J. Biol. Chem. 256 : 1480-1485
170.Villafranca, J. E., and Robertus, J. D. (1981) Ricin B chain is a product of gene duplication. J. Biol. Chem. 256 : 554-556
171.Lamb, F. I., Roberts, L. M., and Lord, J. M. (1985) Nucleotide sequence of cloned cDNA coding for preproricin. Eur. J. Biochem. 148 : 265-270
172.Habuka, N., Murakami, Y., Noma, M., Kudo, T., and Horikoshi, K. (1989) Amino acid sequence of Mirabilis antiviral protein, total synthesis of its gene and expression in Escherichia coli. J. Biol. Chem. 264 : 6629-6637
173.O'Hare, M., Roberts, L. M., Thorpe, P. E., Watson, G. J., Prior, B., and Lord, J. M. (1987) Expression of ricin A chain in Escherichia coli. FEBS Lett. 216 : 73-78
174.Wawrznczak, E. J., (1991) Systemic immunotoxic therapy of cancer: advances and prospects. Br. J. Cancer 64 : 624-630
175.Shaw, P. C., Wong, K. B., Li, X. B., Yeung, H. W., and Ng, T. B. (1992) Mutagenesis of trichosanthin, a ribosome-inactivating protein. The Intl Sym. on Immunotoxins: pp. 50, Sheraton World Restort, Orlando, Florida.
176.Chow, L. P., Chou, M. H., Ho, C.Y., Chuang, C. C., Pan, F. M., Wu, S. H., and Lin, J. Y. (1999) Purification, characterization and molecular cloning of trichoanguin, a novel type I ribosome-inactivating protein from the seeds of Trichosanthes anguina. Biochem. J. 338 : 211-219
177.Somasekaram, A., Jarmuz, A., How, A., Scott, J., and Navaratnam, N. (1999) Intracellular localization of human cytidine deaminase. J. Biol. Chem. 274 : 28405-28412