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Independency of anti-HIV-1 activity from ribosome-inactivating activity of trichosanthin.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2003 Feb 28; Vol. 302 (1), pp. 89-94. - Publication Year :
- 2003
-
Abstract
- Trichosanthin (TCS) is a type I ribosome-inactivating (RI) protein possessing multiple biological and pharmacological activities. Its major action is inhibition of human immunodeficiency virus (HIV) replication but the mechanism is still elusive. All evidences showed that this action is related to its RI activity. Previous studies found that TCS mutants with reduced RI activity simultaneously lost some anti-HIV activity. In this study, an exception was demonstrated by two TCS mutants retaining almost all RI activity but were devoid of anti-HIV-1 activity. Five mutants were constructed by using site-directed mutagenesis with either deletion or addition of amino acids to the C-terminal sequence. Results showed that the RI activity of mutants with C-terminal deletion mutants (TCS(C2), TCS(C4), and TCS(C14)) decreased by 1.2-3.3-fold with parallel downshifting of its anti-HIV-1 activity (1.4-4.8-fold). Another two mutants, TCS(C19aa) and TCS(KDEL) having 19 amino acid extension and a KDEL signal sequence added to the C-terminal sequence, retained all RI activity but subsequently lost most of the anti-HIV-1 activity. These findings suggested that ribosome inactivation alone might not be adequate to explain the anti-HIV action of TCS.
- Subjects :
- Amino Acid Sequence
Anti-HIV Agents chemistry
Cell Line
Enzyme-Linked Immunosorbent Assay
HIV-1 physiology
Humans
Molecular Sequence Data
Mutagenesis, Site-Directed
Trichosanthin chemistry
Virus Replication drug effects
Anti-HIV Agents pharmacology
HIV-1 drug effects
Ribosomes drug effects
Trichosanthin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 302
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 12593852
- Full Text :
- https://doi.org/10.1016/s0006-291x(03)00119-0