Document 0895
 DOCN  M9460895
 TI    Proteolytic processing mechanisms of a miniprecursor of the aspartic
       protease of human immunodeficiency virus type 1.
 DT    9404
 AU    Co E; Koelsch G; Lin Y; Ido E; Hartsuck JA; Tang J; Protein Studies
       Program, Oklahoma Medical Research Foundation,; Oklahoma City 73104.
 SO    Biochemistry. 1994 Feb 8;33(5):1248-54. Unique Identifier : AIDSLINE
       MED/94153911
 AB    The infectivity of the human immunodeficiency virus (HIV) depends upon
       correct proteolytic processing of viral polyprotein precursors, the
       Pr55gag and Pr160gag-pol polyproteins. The processing is mediated
       spontaneously by the viral protease unit (PR) contained within the
       Pr160gag-pol precursor. However, little is known about the mechanism of
       this process. The expression in Escherichia coli and the isolation of a
       14-kDa HIV-1 PR miniprecursor with Ala28 mutated to serine has permitted
       study of the mechanism for cleavage at the N-terminus of the protease.
       The miniprecursor is active against a synthetic peptide substrate, and
       its specific activity is near that of the mutant mature protease. The
       rate of conversion of radiolabeled precursor to mature protease is
       quantitated by measuring the amounts of the two radiolabeled proteins
       separated by SDS-PAGE. The apparent first-order conversion rate
       constant, kapp, is dependent on miniprecursor concentration indicating a
       second-order reaction and suggesting an interdimeric processing
       mechanism. A significant first-order rate constant is observed when the
       plot of kapp versus initial precursor concentration is extrapolated to
       zero. This observation suggests the presence of an alternative
       processing mechanism involving a single active precursor dimer. The
       presence of both mechanisms is an advantage for the virus to ensure
       processing under various conditions.
 DE    Amino Acid Sequence  Aspartic Acid/METABOLISM  Enzyme
       Precursors/METABOLISM  Hydrolysis  HIV Protease/*METABOLISM
       HIV-1/ENZYMOLOGY  Kinetics  Molecular Sequence Data  *Protein
       Processing, Post-Translational  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  JOURNAL ARTICLE

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