Premium
Modelling, synthesis and biological activity of a BLV proteinase, made of (only) 116 amino acids
Author(s) -
Précigoux G.,
Geoffre S.,
Léonard R.,
Llido S.,
Dautant A.,
d'Estaintot B.Langlois,
Picard P.,
Ménard A.,
Guillemain B.,
Hospital M.
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)81798-5
Subject(s) - rous sarcoma virus , amino acid , virology , bovine leukemia virus , peptide sequence , protease , biology , virus , peptide , proteolytic enzymes , biochemistry , microbiology and biotechnology , enzyme , chemistry , gene
Bovine leukaemia virus (BLV) is the aetiological agent of Leukosis enzootica bovis [Viral Oncology (1980), G. Klein (Ed.) Raven Press, New York, pp. 231–238], a widely spread disease in cattle. BLV is reported as the animal model of human T‐cell leukaemia virus (HLTV) which is the causative agent of adult T‐cell leukaemia and tropical spastic paraparesis. Like the viruses themselves, the two retroviral proteinases (PR) are very closely related [Virology 142 (1985) 357–377]. BLV and HTLV‐I PR are reported as putative proteins made of 126 [J. Virol. 57 (1986) 826 832] and 125 [FEBS Lett. 293 (1991) 106–110] amino acids, respectively ( long sequences ), belonging to the aspartyl proteinase family [Nature 329 (1987) 351–354] with the aid of molecular modelling, we show that BLV and HLTV‐I proteinases made of only 116 and 115 amino acids, respectively ( short sequences ), display three‐dimensional structures similar to that observed for other retroviral aspartyl proteinases. The models are based on three‐dimensional structures of the Rous sarcoma virus (RSV PR) and the human immunodeficiency virus (HIV‐I PR). We used solid phase peptide synthesis to produce the putative proteolytic enzyme of BLV (116 amino acids). In this study, we show that the folded synthetic protease accurately hydrolyzes a decapeptide corresponding to the sequence of the Matrice—Capside (MA/CA) cleavage site of the gag polyprotein. In addition, the proteolytic activity is inhibited by a statine ((4 S ,3 S )‐4‐amino‐3‐hydroxyl‐6‐methylheptanoic acid) containing an analogous sequence.