Abstract
Two models for prediction of the activity and stability of site-directed mutagenesis on tumor necrosis factor-α are established. The models are based on straightforward structural considerations, which do not require the elaboration of sitedirected mutagenesis on the protein core and the hydrophobic surface area by analyzing the pmperties of the mutated amino acid residues. The reliabilities of the models have been tested by analyzing the mutants of tumor necrosis factor-α (TNF-α) whose two leucine residues (L29, L157) were mutated. Based on these models, a TNFα mutant with high activity was created by molecular design.
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References
van Gunsteren, W. F., Mark, A. E., Prediction of the activity and stability effects of site-directed mutagenesis on a protein core.J. Mol. Biol., 1992, 227: 389.
Jones, E. Y., Structure of tumor necrosis factor, inTumor Necrosis Factor (eds. Aggarwal, B. B., Vilcek, J.), New York: Marcel Dekker, Inc., 1992, 93–127.
Zhang, X. M., Weber, I., Chen, M. J., Site-directed mutational analysis of human tumor necrosis factor-α,J. Biol. Chem., 1992, 267: 24069.
Van Ostade, X., Tavernier, J., Fiers, W., Structure-activity studies human tumour necrosis factors,Protein Engng., 1994, 7(1): 5.
Yamagishi, J., Kawmhima, H., Maisuo, N.et al., Mutational analysis of structure activity relationships in human tumor necrosis factor-alpha.Protein Engng., 1990. 3: 713.
Nakamura, S., Masegi, T., Kitai, K.et al., Extmcelluar production of humen tumor necrosis factor-α byEscherichia coli using a chemically-synthesized gene,Agricult. Biol. Chem., 1990. 54: 3241.
Creasey, A. A., Doyle, L. V., Reynolds, M. T.et al., Biological effects of recombinant human tumor necrosis factor and its novel mutants on tumor and normal cell lines,Cancer Res., 1987, 47: 145.
Tsujimoto, M., Tanaka, S., Sakuragawa, Y.et al., Comparative studies of the biological activities of human tumor necrosis factor and its derivatives,J. Biochem., 1987, 101: 919.
Nakamura, S., Masegi, T., Fukuoka, M.et al., Interactions between novel tumor necrosis factor-α mutants and receptors on tumor and normal cells,Agricult. Biol. Chem., 1991, 55: 53.
Mark, D. F., Wang, A., Levenson, C.,Methods Engymol., 1987, 154: 403.
Jones, E. Y., Stuart, D. I., Walker, N. P. C., Structure of tumour necrosis factor,Nature, 1989, 338: 225.
Goh, C. R., Porter, A. G., Structural and functional domains in human tumour necrosis factors,Protein Engng., 1991, 4: 385.
Eck, M. J., Sprang, S. R., The structure of tumor necrosis factor-α at 2.6 Å resolution.J. Biol. Chem., 1989. 264: 17595.
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Project supported by the Chinese National High Technology Development Program.
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Tang, W., Xi, T., Wang, B. et al. Prediction of mutant activity and its application in molecular design of tumor necrosis factor-α. Sci. China Ser. C.-Life Sci. 40, 1–9 (1997). https://doi.org/10.1007/BF02879101
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DOI: https://doi.org/10.1007/BF02879101