Characterization of intermediates in the oxidation of zinc fingers in human immunodeficiency virus type 1 nucleocapsid protein P7. NLM AIDSLINE Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

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Characterization of intermediates in the oxidation of zinc fingers in human immunodeficiency virus type 1 nucleocapsid protein P7.

Drug Metab Dispos. 1996 Dec;24(12):1395-400. Unique Identifier : AIDSLINE MED/97126224
Hathout Y; Fabris D; Han MS; Sowder RC 2nd; Henderson LE; Fenselau C; Structural Biochemistry Center, University of Maryland Baltimore; County, 21250, USA.

Abstract: Oxidants targeted toward inactivation of the nucleocapsid zinc finger protein are under development as antiviral agents, especially for use against human immunodeficiency virus. In the present study, electrospray ionization-mass spectrometry is used to follow in situ the progress of the reactions of 2,2'-dithiodipyridine and disulfiram with recombinant nucleocapsid protein p7 (Ncp7) from human immunodeficiency virus-1 at pH 7.4. Both reagents react with the two zinc fingers in the protein, resulting in the ejection of two zinc ions and the formation of oxidized apo-Ncp7 with three intramolecular disulfide bonds. The ejection of zinc by 2,2'-dithiodipyridine occurs in two steps. Alkylation of unreacted cysteine residues with N-ethylmaleimide after a 2-min reaction with 2,2'-dithiodipyridine reveals that the carboxyl-terminal zinc finger is disrupted first. Cys-49, Cys-36, and, to a lesser extent, Cys-39 are all shown to be target residues for initial electrophilic attack. In the reaction of disulfiram with Ncp7, ejection of the two zinc ions also occurs in two steps; however, the fully oxidized apo-Ncp7 is formed more rapidly. Thus, after a 40-min reaction, 45% of native Ncp7 is oxidized by 2,2'-dithiodipyridine, whereas 75% is oxidized by disulfiram.
Keywords: *Capsid/CHEMISTRY *Gene Products, gag/CHEMISTRY *HIV-1/CHEMISTRY *Zinc Fingers/DRUG EFFECTSKWDcapsid/chemistryKWDgeneproducts,gag/chemistryKWDhiv-1/chemistryKWDzincfingers/drugeffects
970630
M9761164

Copyright © 1997 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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