Sub‐site preferences of the aspartic proteinase from the human immunodeficiency virus, HIV‐1

FEBS Letters

Phylip, Lowri H.²  Dunn, Ben M.³  Velek, Jiri¹  Konvalinka, Jan¹  Kostka, Vladimir¹  Strop, Petr¹  Cerna, Vera¹  Richards, Anthony D.²  Kay, John² 

[1] Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Science, Flemingovo namesti 2, 16610 Praha 6, Czechoslovakia;Department of Biochemistry, University of Wales College of Cardiff, PO Box 903, Cardiff CF1 1ST, Wales, UK;Department of Biochemistry and Molecular Biology, J. Hillis Miller Health Centre, University of Florida, Gainesville, FL 32610, USA

关键词: HIV-1 proteinase;    Chromogenic substrate;    Subsite;    Specificity;    Nle;    norleucine;    Nph;    4-NO2-phenylalanine (The nomenclature system of Schechter and Berger [12];    i.e. P5-P4-P3-P2-P1 ∗P1́-P2́-P3́ is used to depict amino acids adjacent to the residues in the P1 and P1́ positions which contribute the scissile peptide bond (indicated by an asterisk ∗));   

DOI  :  10.1016/0014-5793(90)80966-M

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A series of synthetic, chromogenic substrates for HIV-1 proteinase with the general structure Ala-Thr-His-Xaa-Yaa-Zaa∗Nph-Val-Arg-Lys-Ala was synthesised with a variety of residues introduced into the Xaa, Yaa and Zaa positions. Kinetics parameters for hydrolysis of each peptide by HIV-1 proteinase at pH 4.7, 37°C and u = 1.0 M were measured spectrophotometrically and/or by reverse phase FPLC. A variety of residues was found to be acceptable in the P₃, position whilst hydrophobic/aromatic residues were preferable in P₁. The nature of the residue occupying the P₂; position had a strong influence on k _cat (with little effect on k _m;β-branched residues Val or Ile in this position resulted in considerably faster peptide hydrolysis than when e.g. the Leu-containing analogue was present in P₂.

【 授权许可】

Unknown