Modelling, synthesis and biological activity of a BLV proteinase, made of (only) 116 amino acids

FEBS Letters

Geoffre, S.¹  Llido, S.¹  Précigoux, G.¹  Hospital, M.¹  Dautant, A.¹  Guillemain, B.²  d'Estaintot, B.Langlois¹  Ménard, A.²  Picard, P.¹  Léonard, R.¹ 

[1] Laboratoire de Cristallographie, URA 144 CNRS, Université de Bordeaux I, 351 cours de la Libération, 33405 - Talence Cedex, France;Fondation Bergonié, INSERM 328, Université de Bordeaux, 229 cours de l'Argonne, 33076 - Bordeaux Cedex, France

关键词: BLV protease;    Modelling;    Solid phase synthesis;    Protease activity and inhibition;   

DOI  :  10.1016/0014-5793(93)81798-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 ((4S,3S)-4-amino-3-hydroxyl-6-methylheptanoic acid) containing an analogous sequence.

【 授权许可】

Unknown