In vitro and in silico binding study of the peptide derived from HIV-1 CA-CTD and LysRS as a potential HIV-1 blocking site

Nakorn, Poonsap Na; Treesuwan, Witcha; Choowongkomon, Kiattawee; Hannongbua, Supa; Boonyalai, Nonlawat

doi:10.1016/j.jtbi.2010.11.010

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…More recently, an ab initio energy minimized "bridging monomer" model of the HIV-1 CA-CTD⅐LysRS⅐tRNA Lys ternary complex has been proposed, which is also consistent with an interaction between helix 4 of CA-CTD and the H7 region of LysRS (23). In addition, circular dichroism experiments along with in silico studies also support this helix 4/H7 interaction (24).…”

supporting

confidence: 53%

Dual Role for Motif 1 Residues of Human Lysyl-tRNA Synthetase in Dimerization and Packaging into HIV-1

Dewan

Wei

Kleiman

et al. 2012

Journal of Biological Chemistry

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supporting

confidence: 53%

Dual Role for Motif 1 Residues of Human Lysyl-tRNA Synthetase in Dimerization and Packaging into HIV-1

Dewan

Wei

Kleiman

et al. 2012

Journal of Biological Chemistry

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“…More recently, Schimmel and co-workers have produced an ab initio energy minimized “bridging monomer” model of the HIV-1 CA-CTD/hLysRS/tRNA Lys ternary complex (Figure ). Furthermore, circular dichroism experiments along with in silico binding studies support an interaction between h4 of the CA-CTD and helix 7 of the motif 1 domain of hLysRS . Taken together, these data suggest that targeting the h4 region of the CA-CTD, which forms the interface with hLysRS, is another potential drug target.…”

mentioning

confidence: 65%

mentioning

confidence: 85%

“…Furthermore, circular dichroism experiments along with in silico binding studies support an interaction between h4 of the CA-CTD and helix 7 of the motif 1 domain of hLysRS. 26 Taken together, these data suggest that targeting the h4 region of the CA-CTD, which forms the interface with hLysRS, is another potential drug target. Previous attempts to develop inhibitors against CA led to the identification of a variety of small molecule inhibitors, namely, CAP-1, 27 CAP-2, 27 PA-457, 28 and PF-3450074.…”

mentioning

confidence: 85%

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Cyclic Peptide Inhibitors of HIV-1 Capsid-Human Lysyl-tRNA Synthetase Interaction

et al. 2012

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The human immunodeficiency virus type 1 (HIV-1) capsid protein (CA) plays a critical role in the viral life cycle. The C-terminal domain (CTD) of CA binds to human lysyl-tRNA synthetase (hLysRS), and this interaction facilitates packaging of host cell tRNALys,3, which serves as the primer for reverse transcription. Here, we report the library synthesis, high-throughput screening, and identification of cyclic peptides (CPs) that bind HIV-1 CA. Scrambling or single-residue changes of the selected peptide sequences eliminated binding, suggesting a sequence-specific mode of interaction. Two peptides (CP2 and CP4) subjected to detailed analysis also inhibited hLysRS/CA interaction in vitro. Nuclear magnetic resonance spectroscopy and mutagenesis studies revealed that both CPs bind to a site proximal to helix 4 of the CA-CTD, which is the known site of hLysRS interaction. These results extend the current repertoire of CA-binding molecules to a new class of peptides targeting a novel site with potential for development into novel antiviral agents.

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“…A number of other cellular factors interact with Gag and play various roles in virus production ( Table 1 ). For instance, the tRNA Lys synthetase interacts with the CA domain, helping the recruitment of tRNA Lys into HIV-1 virions [ 278 , 279 , 280 , 281 , 282 ]. CypA interacts with the CA domain, modulating the maturation of virus particles [ 96 , 250 , 251 , 252 , 253 ] and the clathrin adaptor protein complexes AP-1, AP-2, and AP-3 interact with the MA domain of Gag, participating in Gag trafficking and virus release [ 234 , 235 , 236 ].…”

Section: Interactions Involving the Nc Domain Of Gagmentioning

confidence: 99%

How HIV-1 Gag Manipulates Its Host Cell Proteins: A Focus on Interactors of the Nucleocapsid Domain

Klingler

Anton

Réal

et al. 2020

Viruses

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The human immunodeficiency virus (HIV-1) polyprotein Gag (Group-specific antigen) plays a central role in controlling the late phase of the viral lifecycle. Considered to be only a scaffolding protein for a long time, the structural protein Gag plays determinate and specific roles in HIV-1 replication. Indeed, via its different domains, Gag orchestrates the specific encapsidation of the genomic RNA, drives the formation of the viral particle by its auto-assembly (multimerization), binds multiple viral proteins, and interacts with a large number of cellular proteins that are needed for its functions from its translation location to the plasma membrane, where newly formed virions are released. Here, we review the interactions between HIV-1 Gag and 66 cellular proteins. Notably, we describe the techniques used to evidence these interactions, the different domains of Gag involved, and the implications of these interactions in the HIV-1 replication cycle. In the final part, we focus on the interactions involving the highly conserved nucleocapsid (NC) domain of Gag and detail the functions of the NC interactants along the viral lifecycle.

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In vitro and in silico binding study of the peptide derived from HIV-1 CA-CTD and LysRS as a potential HIV-1 blocking site

Cited by 6 publications

References 27 publications

Dual Role for Motif 1 Residues of Human Lysyl-tRNA Synthetase in Dimerization and Packaging into HIV-1

Dual Role for Motif 1 Residues of Human Lysyl-tRNA Synthetase in Dimerization and Packaging into HIV-1

Cyclic Peptide Inhibitors of HIV-1 Capsid-Human Lysyl-tRNA Synthetase Interaction

How HIV-1 Gag Manipulates Its Host Cell Proteins: A Focus on Interactors of the Nucleocapsid Domain

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