       Document 0545
 DOCN  M9630545
 TI    Mutational analysis of the substrate binding pocket of murine leukemia
       virus protease and comparison with human immunodeficiency virus
       proteases.
 DT    9603
 AU    Menendez-Arias L; Weber IT; Oroszlan S; Centro de Biologia Molecular
       Severo Ochoa, Consejo Superior de; Investigaciones
       Cientificas-Universidad Autonoma de Madrid,; Spain.
 SO    J Biol Chem. 1995 Dec 8;270(49):29162-8. Unique Identifier : AIDSLINE
       MED/96094303
 AB    The differences in substrate specificity between Moloney murine leukemia
       virus protease (MuLV PR) and human immunodeficiency virus (HIV) PR were
       investigated by site-directed mutagenesis. Various amino acids, which
       are predicted to form the substrate binding site of MuLV PR, were
       replaced by the equivalent ones in HIV-1 and HIV-2 PRs. The expressed
       mutants were assayed with the substrate Val-Ser-Gln-Asn-Tyr decreases
       Pro-Ile-Val-Gln-NH2 (decreases indicates the cleavage site) and a series
       of analogs containing single amino acid substitutions in positions
       P4(Ser) to P3'(Val). Mutations at the predicted S2/S2' subsites of MuLV
       PR have a strong influence on the substrate specificity of this enzyme,
       as observed with mutants H37D, V39I, V54I, A57I, and L92I. On the other
       hand, substitutions at the flap region of MuLV PR often rendered enzymes
       with low activity (e.g. W53I/Q55G). Three amino acids (His-37, Val-39,
       and Ala-57) were identified as the major determinants of the differences
       in substrate specificity between MuLV and HIV PRs.
 DE    Amino Acid Sequence  Base Sequence  Binding Sites  Comparative Study
       HIV Protease/*CHEMISTRY/METABOLISM  Leukemia Viruses, Murine/*ENZYMOLOGY
       Molecular Sequence Data  Mutagenesis, Site-Directed  Peptide
       Peptidohydrolases/*CHEMISTRY  Structure-Activity Relationship  Substrate
       Specificity  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Viral
       Proteins/*CHEMISTRY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

