Science in China Series C: Life Sciences

, Volume 40, Issue 1, pp 1–9 | Cite as

Prediction of mutant activity and its application in molecular design of tumor necrosis factor-α

  • Weidong Tang
  • Tao Xi
  • Bo Wang
  • Donglin Guo
  • Xianxiu Xu
  • Dexu Zhu
Article

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.

Keywords

prediction model tumor neauwia factor-α molecular design 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    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.PubMedCrossRefGoogle Scholar
  2. 2.
    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.Google Scholar
  3. 3.
    Zhang, X. M., Weber, I., Chen, M. J., Site-directed mutational analysis of human tumor necrosis factor-α,J. Biol. Chem., 1992, 267: 24069.PubMedGoogle Scholar
  4. 4.
    Van Ostade, X., Tavernier, J., Fiers, W., Structure-activity studies human tumour necrosis factors,Protein Engng., 1994, 7(1): 5.CrossRefGoogle Scholar
  5. 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.CrossRefGoogle Scholar
  6. 6.
    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.Google Scholar
  7. 7.
    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.PubMedGoogle Scholar
  8. 8.
    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.PubMedGoogle Scholar
  9. 9.
    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.Google Scholar
  10. 10.
    Mark, D. F., Wang, A., Levenson, C.,Methods Engymol., 1987, 154: 403.CrossRefGoogle Scholar
  11. 11.
    Jones, E. Y., Stuart, D. I., Walker, N. P. C., Structure of tumour necrosis factor,Nature, 1989, 338: 225.PubMedCrossRefGoogle Scholar
  12. 12.
    Goh, C. R., Porter, A. G., Structural and functional domains in human tumour necrosis factors,Protein Engng., 1991, 4: 385.CrossRefGoogle Scholar
  13. 13.
    Eck, M. J., Sprang, S. R., The structure of tumor necrosis factor-α at 2.6 Å resolution.J. Biol. Chem., 1989. 264: 17595.PubMedGoogle Scholar

Copyright information

© Science in China Press 1997

Authors and Affiliations

  • Weidong Tang
    • 1
  • Tao Xi
    • 1
  • Bo Wang
    • 1
  • Donglin Guo
    • 1
  • Xianxiu Xu
    • 1
  • Dexu Zhu
    • 1
  1. 1.Department of Biochemistry and State Key Laboratory of Pharmaceutical BiotechnologyNanjing UniversityNanjingChina

Personalised recommendations