Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Biochimie ; 79(11): 673-80, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9479450

ABSTRACT

The Gag-encoded nucleocapsid protein NCp7 (72 amino acids) from HIV-1, the regulatory protein, Vpr (96 amino acids) and numerous derivatives have been synthesized by solid phase method and their structures determined by 2D NMR. In NCp7, the two highly folded zinc fingers of the Cx2Cx4Hx4C type are in close spacial proximity and the replacement of H by C in the first zinc finger or P by L in the short interdigital domain led to structural modifications evidenced by NMR. In vivo, these point mutations induced a complete loss of viral infectivity by interrupting critical step(s) of the retroviral life cycle. To account for these findings, a model of the complex between NCp7 and d (ACGCC) has been proposed from NMR data, showing the intercalation of Trp37 in the oligonucleotide. This model could also explain the role of NCp7 in the formation of viral particles and agrees with the modifications in morphology of the virions containing mutations in the NCp7 zinc fingers. Vpr is essentially constituted by two long helical domains at its N- and C-terminals and the side chains of Leu60 and Leu67 participate in a leucine-zipper mode of intramolecular interaction. The results obtained have been used to try to develop new antiviral agents inhibiting NCp7 functions and thus possibly devoid of the resistance effects found with inhibitors of HIV enzymes (reverse transcriptase and protease).


Subject(s)
Capsid Proteins , Capsid/chemistry , Capsid/metabolism , Gene Products, gag/chemistry , Gene Products, gag/metabolism , Gene Products, vpr/chemistry , Gene Products, vpr/metabolism , HIV-1/chemistry , Viral Proteins , Amino Acid Sequence , Animals , Capsid/antagonists & inhibitors , Gene Products, gag/antagonists & inhibitors , Gene Products, vpr/antagonists & inhibitors , Humans , Models, Molecular , Molecular Sequence Data , Structure-Activity Relationship , gag Gene Products, Human Immunodeficiency Virus , vpr Gene Products, Human Immunodeficiency Virus
SELECTION OF CITATIONS
SEARCH DETAIL
...