Document 0082
 DOCN  M94A0082
 TI    Removal of zinc is required for processing of the mature nucleocapsid
       protein of human immunodeficiency virus, type 1, by the viral protease.
 DT    9412
 AU    Wondrak EM; Sakaguchi K; Rice WG; Kun E; Kimmel AR; Louis JM; Laboratory
       of Cellular and Developmental Biology, NIDDK, National; Institutes of
       Health, Bethesda, Maryland 20892.
 SO    J Biol Chem. 1994 Sep 2;269(35):21948-50. Unique Identifier : AIDSLINE
       MED/94350935
 AB    In human immunodeficiency virus, RNA selection and packaging during
       assembly involve the two retroviral-type fingers of the nucleocapsid
       protein that are held in a constrained configuration by coordinated zinc
       ions. In this report, we demonstrate that the nucleocapsid protein in a
       metal bound state is resistant to cleavage by the viral protease, but
       upon removal of zinc ions by chelating agents, it is hydrolyzed within
       the first zinc finger between Phe-16 and Asn-17. However,
       3-nitrosobenzamide and cupric ions, which release zinc through oxidation
       of the cysteine residues of the finger, render the nucleocapsid protein
       resistant to cleavage. Since protease inhibitors and 3-nitrosobenzamide
       restrict processes relating to steps early in infection, the cleavage of
       the nucleocapsid protein may represent an essential event that can be
       exploited for the design of novel antiviral agents.
 DE    Amino Acid Sequence  Benzamides/PHARMACOLOGY  Capsid/*METABOLISM  Gene
       Products, gag/*METABOLISM  HIV Protease/*METABOLISM
       HIV-1/ENZYMOLOGY/*METABOLISM  Molecular Sequence Data  Nitroso
       Compounds/PHARMACOLOGY  *Protein Processing, Post-Translational/DRUG
       EFFECTS  Support, U.S. Gov't, P.H.S.  Zinc/*METABOLISM  *Zinc Fingers
       JOURNAL ARTICLE

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