Journal of Biological Chemistry 1994-09-02

Removal of zinc is required for processing of the mature nucleocapsid protein of human immunodeficiency virus, type 1, by the viral protease.

E M Wondrak, K Sakaguchi, W G Rice, E Kun, A R Kimmel, J M Louis

Index: J. Biol. Chem. 269(35) , 21948-50, (1994)

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Abstract

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.

Related Compounds

  • 3-nitrosobenzamide

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