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Effect of substrate residues on the P2 ' preference of retroviral proteinases

  1. Author:
    Boross, P.
    Bagossi, P.
    Copeland, T. D.
    Oroszlan, S.
    Louis, J. M.
    Tozser, J.
  2. Author Address

    Tozser J Debrecen Univ Med, Sch Med, Dept Biochem & Mol Biol POB 6 H-4012 Debrecen Hungary Debrecen Univ Med, Sch Med, Dept Biochem & Mol Biol H-4012 Debrecen Hungary NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Special Program Prot Chem Frederick, MD USA NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mol Virol & Carcinogenesis Lab Frederick, MD USA NIDDKD, Phys Chem Lab, NIH Bethesda, MD 20892 USA
    1. Year: 1999
  1. Journal: European Journal of Biochemistry
    1. 264
    2. 3
    3. Pages: 921-929
  2. Type of Article: Article
  1. Abstract:

    The substrate sequence requirements for preference toward P2 ' Glu residue by human immunodeficiency virus type 1 (HIV-l) proteinase were studied in both the matrix protein/ capsid protein (MA/CA) and CA/p2 cleavage site sequence contexts. These sequences represent typical type 1 (-aromatic*Pro-) and type 2 (-hydrophobic* hydrophobic-) cleavage site sequences, respectively. While in the type 1 sequence context, the preference for P2 ' Glu over Ile or Gin was found to be strongly dependent on the ionic strength and the residues being outside the P2-P2 ' region of the substrate, it remained preferable in the type 2 substrates when typical type 1 substrate sequence residues were substituted into the outside regions. The pH profile of the specificity constants suggested a lower pH optimum for substrates having P2 ' Glu in contrast to those having uncharged residues, in both sequence contexts. The very low frequency of P2 ' Glu in naturally occurring retroviral cleavage sites of various retroviruses including equine infectious anemia virus (EIAV) and murine leukemia virus (MuLV) suggests that such a residue may not have a general regulatory role in the retroviral life cycle. In fact, unlike HN-I and HIV-2, EIAV and MuLV proteinases do not favor P2 ' Glu in either the MA/CA or CA/p2 sequence contexts. [References: 43]

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