Document 0636
 DOCN  M9650636
 TI    Complete inhibition of human immunodeficiency virus Gag myristoylation
       is necessary for inhibition of particle budding.
 DT    9605
 AU    Morikawa Y; Hinata S; Tomoda H; Goto T; Nakai M; Aizawa C; Tanaka H;
       Omura S; Kitasato Institute, Tokyo, Japan.
 SO    J Biol Chem. 1996 Feb 2;271(5):2868-73. Unique Identifier : AIDSLINE
       MED/96162038
 AB    Myristoylation of human immunodeficiency virus (HIV) Gag protein is
       essential for virus particle budding. Two reactions are involved;
       activation of free myristate to myristoyl-CoA and transfer of the
       myristoyl residue to the Gag N-terminal glycine. We have investigated
       the effects of triacsin C, an inhibitor of long chain acyl-CoA
       synthetase, on release of HIV Gag virus-like particle (VLP) produced
       using the recombinant baculovirus system. First, inhibition of acyl-CoA
       formation by triacsin C was confirmed using the membrane fractions of
       insect Sf9 cells as an enzyme source. Second, when HIV Gag protein was
       expressed in the presence of triacsin C (0-48 microM), Gag
       myristoylation was inhibited in a dose-dependent manner. Budding of Gag
       VLP, however, did not follow similar inhibition kinetics but appeared
       unaffected up to 24 microM, yet was completely abolished at 48 microM
       when the myristoylation of Gag protein was also completely inhibited.
       The all-or-none inhibition of Gag VLP budding suggests that although
       inhibition of acyl-CoA synthetase blocks the production of myristoylated
       Gag protein, only complete inhibition of Gag myristoylation prevents VLP
       budding. Thus, relatively few myristoylated Gag molecules are sufficient
       for plasma membrane targeting and VLP budding.
 DE    Acyl Coenzyme A/BIOSYNTHESIS  Animal  Cell Line  Coenzyme A
       Synthetases/ANTAGONISTS & INHIB  Enzyme Inhibitors/PHARMACOLOGY  Gene
       Products, gag/GENETICS/*METABOLISM  HIV/*METABOLISM  Microscopy,
       Electron  Myristic Acids/*ANTAGONISTS & INHIB  Nuclear Polyhedrosis
       Virus/GENETICS  Spodoptera  Support, Non-U.S. Gov't
       Triazenes/PHARMACOLOGY  Virion/DRUG EFFECTS/PHYSIOLOGY  JOURNAL ARTICLE

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