scholarly journals Experimental data of Extremely thermostabilizing core mutations in coiled-coil mi-metic proteins of HIV-1 gp41 produce diverse effects on target binding and inhibitory activity

Datasets ◽  
2021 ◽  
Author(s):  
Mario Cano-Muñoz
Keyword(s):  
Experimental Data ◽  
Inhibitory Activity ◽  
Coiled Coil ◽  
Target Binding ◽  
Hiv 1

scholarly journals Crystal structure of the simian immunodeficiency virus (SIV) gp41 core: Conserved helical interactions underlie the broad inhibitory activity of gp41 peptides

1998 ◽  
Vol 95 (16) ◽  
pp. 9134-9139 ◽  
Author(s):  
Vladimir N. Malashkevich ◽  
David C. Chan ◽  
Christine T. Chutkowski ◽  
Peter S. Kim
Keyword(s):  
Crystal Structure ◽  
Viral Entry ◽  
Inhibitory Activity ◽  
Potent Inhibitor ◽  
Coiled Coil ◽  
Gp41 Ectodomain ◽  
Peptide Analogs ◽  
Immunodeficiency Virus ◽  
Packing Interactions ◽  
Hiv 1

The gp41 subunit of the envelope protein complex from human and simian immunodeficiency viruses (HIV and SIV) mediates membrane fusion during viral entry. The crystal structure of the HIV-1 gp41 ectodomain core in its proposed fusion-active state is a six-helix bundle. Here we have reconstituted the core of the SIV gp41 ectodomain with two synthetic peptides called SIV N36 and SIV C34, which form a highly helical trimer of heterodimers. The 2.2 Å resolution crystal structure of this SIV N36/C34 complex is very similar to the analogous structure in HIV-1 gp41. In both structures, three N36 helices form a central trimeric coiled coil. Three C34 helices pack in an antiparallel orientation into highly conserved, hydrophobic grooves along the surface of this coiled coil. The conserved nature of the N36-C34 interface suggests that the HIV-1 and SIV peptides are functionally interchangeable. Indeed, a heterotypic complex between HIV-1 N36 and SIV C34 peptides is highly helical and stable. Moreover, as with HIV-1 C34, the SIV C34 peptide is a potent inhibitor of HIV-1 infection. These results identify conserved packing interactions between the N and C helices of gp41 and have implications for the development of C peptide analogs with broad inhibitory activity.

scholarly journals Extremely Thermostabilizing Core Mutations in Coiled-Coil Mimetic Proteins of HIV-1 gp41 Produce Diverse Effects on Target Binding but Do Not Affect Their Inhibitory Activity

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 566
Author(s):  
Mario Cano-Muñoz ◽  
Samuele Cesaro ◽  
Bertrand Morel ◽  
Julie Lucas ◽  
Christiane Moog ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Coiled Coil ◽  
Helical Structure ◽  
Heptad Repeat ◽  
Single Chain ◽  
Cell Infection ◽  
Polar Residues ◽  
Hiv 1

A promising strategy to neutralize HIV-1 is to target the gp41 spike subunit to block membrane fusion with the cell. We previously designed a series of single-chain proteins (named covNHR) that mimic the trimeric coiled-coil structure of the gp41 N-terminal heptad repeat (NHR) region and potently inhibit HIV-1 cell infection by avidly binding the complementary C-terminal heptad repeat (CHR) region. These proteins constitute excellent tools to understand the structural and thermodynamic features of this therapeutically important interaction. Gp41, as with many coiled-coil proteins, contains in core positions of the NHR trimer several highly conserved, buried polar residues, the role of which in gp41 structure and function is unclear. Here we produced three covNHR mutants by substituting each triad of polar residues for the canonical isoleucine. The mutants preserve their helical structure and show an extremely increased thermal stability. However, increased hydrophobicity enhances their self-association. Calorimetric analyses show a marked influence of mutations on the binding thermodynamics of CHR-derived peptides. The mutations do not affect however the in vitro HIV-1 inhibitory activity of the proteins. The results support a role of buried core polar residues in maintaining structural uniqueness and promoting an energetic coupling between conformational stability and NHR–CHR binding.

A Novel Ribonuclease with HIV-1 Reverse Transcriptase Inhibitory Activity from the Edible Mushroom Hygrophorus russula

2013 ◽  
Vol 170 (1) ◽  
pp. 219-230 ◽  
Author(s):  
Mengjuan Zhu ◽  
Lijing Xu ◽  
Xiao Chen ◽  
Zengqiang Ma ◽  
Hexiang Wang ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Inhibitory Activity ◽  
Edible Mushroom ◽  
Hiv 1

Synthesis and HIV-1 integrase inhibitory activity of dimeric and tetrameric analogs of indolicidin

2004 ◽  
Vol 14 (22) ◽  
pp. 5595-5598 ◽  
Author(s):  
Krzysztof Krajewski ◽  
Christophe Marchand ◽  
Ya-Qiu Long ◽  
Yves Pommier ◽  
Peter P. Roller
Keyword(s):  
Inhibitory Activity ◽  
Hiv 1

scholarly journals Novel TRIM5 Isoforms Expressed by Macaca nemestrina

2007 ◽  
Vol 81 (22) ◽  
pp. 12210-12217 ◽  
Author(s):  
Greg Brennan ◽  
Yury Kozyrev ◽  
Toshiaki Kodama ◽  
Shiu-Lok Hu
Keyword(s):  
Coiled Coil ◽  
Macaca Nemestrina ◽  
Cdna Clones ◽  
Reading Frame ◽  
Spry Domain ◽  
Immunodeficiency Virus ◽  
Hiv Type 1 ◽  
Hiv 1

ABSTRACT The TRIM5 family of proteins contains a RING domain, one or two B boxes, and a coiled-coil domain. The TRIM5α isoform also encodes a C-terminal B30.2(SPRY) domain, differences within which define the breadth and potency of TRIM5α-mediated retroviral restriction. Because Macaca nemestrina animals are susceptible to some human immunodeficiency virus (HIV) isolates, we sought to determine if differences exist in the TRIM5 gene and transcripts of these animals. We identified a two-nucleotide deletion (Δ2) in the transcript at the 5′ terminus of exon 7 in all M. nemestrina TRIM5 cDNA clones examined. This frameshift results in a truncated protein of 300 amino acids lacking the B30.2(SPRY) domain, which we have named TRIM5θ. This deletion is likely due to a single nucleotide polymorphism that alters the 3′ splice site between intron 6 and exon 7. In some clones, a deletion of the entire 27-nucleotide exon 7 (Δexon7) resulted in the restoration of the TRIM5 open reading frame and the generation of another novel isoform, TRIM5η. There are 18 amino acid differences between M. nemestrina TRIM5η and Macaca mulatta TRIM5α, some of which are at or near locations previously shown to affect the breadth and potency of TRIM5α-mediated restriction. Infectivity assays performed on permissive CrFK cells stably transduced with TRIM5η or TRIM5θ show that these isoforms are incapable of restricting either HIV type 1 (HIV-1) or simian immunodeficiency virus infection. The expression of TRIM5 alleles incapable of restricting HIV-1 infection may contribute to the previously reported increased susceptibility of M. nemestrina to HIV-1 infection in vivo.

Identification of LOGP Values and Electronegativities As Structural Insights to Model Inhibitory Activity of HIV-1 Capsid Inhibitors - A SVM and MLR Aided QSAR Studies

2012 ◽  
Vol 12 (16) ◽  
pp. 1763-1774 ◽  
Author(s):  
Nishant Sharma ◽  
K.R. Ethiraj ◽  
Mukesh Yadav ◽  
Anuraj Nayarisseri S ◽  
Mona Chaurasiya ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Qsar Studies ◽  
Structural Insights ◽  
Hiv 1
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