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- Title
Mutational analysis of human tumor necrosis factor-a.
- Authors
Hang-Cheol Shin; Kwang-Hwi Cho
- Abstract
To understand the structure-function relationship of human tumor necrosis factor-a (TNF-a), mutational analysis was carried out on the lower regions (regions 1-6) of the molecule. The muteins were prepared as a soluble form by using a chaperonin co-expression system and the cytotoxic activities of the purified muteins were evaluated on TNF-sensitive murine fibrosarcoma L929 cells. Three regions (regions 1, 2&4) were found where mutations significantly influenced the bioactivity. In region 1 (residues 1-10), the number of deleted residues and the positioning of positive charges are important to achieve a maximum activity and in region 4 (residues 84-88), introduction of charged residues in one of the positions 86-88 significantly increased the cytotoxic activity. On the other hand, any mutation introduced in region 2 (residues 37-41) had a deleterious effect. The present study provides a structural basis for the design of highly potent TNF-a as a therapeutic agent.
- Subjects
ANTINEOPLASTIC agents; TUMOR necrosis factors; MOLECULAR chaperones; MACROPHAGES; GROWTH factors; GLYCOPROTEINS; BIOPHARMACEUTICS
- Publication
Biotechnology Letters, 2005, Vol 27, Issue 2, p107
- ISSN
0141-5492
- Publication type
Article
- DOI
10.1007/s10529-004-6937-y