Modelling, synthesis and biological activity of a BLV proteinase, made of (only) 116 amino acids.
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 HTLV-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 Rous sarcoma virus (RSV PR) and the human immunodeficiency virus (HIV-1 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 ((4S,3S)-4-amino-3-hydroxyl-6-methylheptanoic acid) containing an analogous sequence.
Précigoux
G
G
Laboratoire de Cristallographie, URA 144 CNRS, Université de Bordeaux I, Talence, France.
Geoffre
S
S
Léonard
R
R
Llido
S
S
Dautant
A
A
d'Estaintot
B L
BL
Picard
P
P
Ménard
A
A
Guillemain
B
B
Hospital
M
M
D000595:Amino Acid Sequence; D010450:Endopeptidases / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000201:enzymology; D001909:Leukemia Virus, Bovine / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D017510:Protein Folding; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D010450:Endopeptidases