scholarly journals Single-point mutations of hepatitis C virus NS3 that impair p53 interaction and anti-apoptotic activity of NS3

2006 ◽  
Vol 340 (3) ◽  
pp. 792-799 ◽  
Author(s):  
Motofumi Tanaka ◽  
Motoko Nagano-Fujii ◽  
Lin Deng ◽  
Satoshi Ishido ◽  
Kiyonao Sada ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Single Point ◽  
Point Mutations ◽  
Single Point Mutations ◽  
Apoptotic Activity

scholarly journals New real-time-PCR method to identify single point mutations in hepatitis C virus

2016 ◽  
Vol 22 (43) ◽  
pp. 9604 ◽  
Author(s):  
Qian Chen ◽  
Irene Belmonte ◽  
Maria Buti ◽  
Leonardo Nieto ◽  
Damir Garcia-Cehic ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Real Time ◽  
Real Time Pcr ◽  
Single Point ◽  
Point Mutations ◽  
Pcr Method ◽  
Single Point Mutations

scholarly journals Hepatitis C virus NS5A protein interacts with 2′,5′-oligoadenylate synthetase and inhibits antiviral activity of IFN in an IFN sensitivity-determining region-independent manner

2004 ◽  
Vol 85 (4) ◽  
pp. 959-969 ◽  
Author(s):  
Takashi Taguchi ◽  
Motoko Nagano-Fujii ◽  
Masato Akutsu ◽  
Hiroyasu Kadoya ◽  
Shinji Ohgimoto ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Cultured Cells ◽  
Single Point ◽  
Point Mutations ◽  
Hcv Rna ◽  
Structural Protein ◽  
Oligoadenylate Synthetase ◽  
Independent Manner

The non-structural protein 5A (NS5A) of hepatitis C virus (HCV) has been implicated in inhibition of antiviral activity of IFN. While previous studies have suggested an interaction between NS5A and the double-stranded RNA-dependent protein kinase (PKR), the possibility still remains that interaction with another molecule(s) is involved in the NS5A-mediated inhibition of IFN. In the present study, we investigated a possible interaction between NS5A and 2′,5′-oligoadenylate synthetase (2-5AS), another key molecule in antiviral activity. We observed that NS5A physically interacted with 2-5AS in cultured cells, with an N-terminal portion of NS5A [aa 1–148; NS5A(1–148)] and two separate portions of 2-5AS (aa 52–104 and 184–275) being involved in the interaction. Single point mutations at residue 37 of NS5A affected the degree of the interaction with 2-5AS, with a Phe-to-Leu mutation (F37L) augmenting and a Phe-to-Asn mutation (F37N) diminishing it. Virus rescue assay revealed that the full-length NS5A (NS5A-F) and NS5A(1–148), the latter of which contains neither the IFN sensitivity-determining region (ISDR) nor the PKR-binding domain, significantly counteracted the antiviral activity of IFN. Introduction of a F37N mutation into NS5A(1–148) impaired the otherwise more significant IFN-inhibitory activity of NS5A(1–148). It was also found that the F37N mutation was highly disadvantageous for the replication of an HCV RNA replicon. Taken together, our results suggest the possibility that NS5A interacts with 2-5AS and inhibits the antiviral activity of IFN in an ISDR-independent manner.

scholarly journals Resistance Profile of a Hepatitis C Virus RNA-Dependent RNA Polymerase Benzothiadiazine Inhibitor

2003 ◽  
Vol 47 (11) ◽  
pp. 3525-3530 ◽  
Author(s):  
Tammy T. Nguyen ◽  
Adam T. Gates ◽  
Lester L. Gutshall ◽  
Victor K. Johnston ◽  
Baohua Gu ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rna Polymerase ◽  
Single Point ◽  
Point Mutations ◽  
Specific Inhibitor ◽  
Cdna Clones ◽  
Single Mutation ◽  
Rna Dependent Rna Polymerase ◽  
Resistance Profile

ABSTRACT Recently, a benzo-1,2,4-thiadiazine antiviral agent (C21H21N3O4S; compound 4) was shown to be a potent, highly specific inhibitor of the primary catalytic enzyme of the hepatitis C virus (HCV) replicase complex. In this study, we selected for resistance to confirm the mechanism of action for compound 4 in HCV replicon cells. As expected, spontaneous mutations or fluidity in the HCV polymerase (NS5B) coding sequence occurred upon routine passage of the HCV replicon cells in the absence of compound 4. After 1 month of culture in the presence of 10 μM compound 4, or 20 times the 50% inhibitory concentration of the replicon, replicon cells were almost 20-fold less susceptible to compound 4. Twenty-one NS5B cDNA clones were generated from the resistant replicon cells. Five mutations in the 21 NS5B clones were present at frequencies higher than that of control replicon cells, and no clone contained more than a single mutation within the polymerase gene. RNA-dependent RNA polymerase studies using purified recombinant NS5B containing these single point mutations allowed the identification of residue 414 as sufficient for biochemical resistance to compound 4. Further, the contribution of this residue to confer cell-based resistance to compound 4 was validated using a stable recombinant mutant replicon cell line which harbors a methionine-to-threonine change at residue 414. The potential for additional mutations in other nonstructural genes of HCV to contribute to the resistance profile of compound 4 is discussed.

Cupin Variants as Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes

2019 ◽  
Author(s):  
Nobutaka Fujieda ◽  
Miho Yuasa ◽  
Yosuke Nishikawa ◽  
Genji Kurisu ◽  
Shinobu Itoh ◽  
...  
Keyword(s):  
Michael Addition ◽  
In Silico ◽  
Addition Reaction ◽  
Single Point ◽  
Point Mutations ◽  
Unsaturated Ketone ◽  
Michael Addition Reaction ◽  
Beta Barrel ◽  
Cupin Superfamily ◽  
Single Point Mutations

Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded beta-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantio-selective Michael addition reaction of nitroalkanes to an α,β-unsaturated ketone. Moreover, in silico substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.

Single-Point Mutations in Qβ Virus-like Particles Change Binding to Cells

2021 ◽  
Author(s):  
Marisa L. Martino ◽  
Stephen N. Crooke ◽  
Marianne Manchester ◽  
M.G. Finn
Keyword(s):  
Single Point ◽  
Point Mutations ◽  
Virus Like Particles ◽  
Single Point Mutations

MinD directly interacting with FtsZ at the H10 helix suggests a model for robust activation of MinC to destabilize FtsZ polymers

2017 ◽  
Vol 474 (18) ◽  
pp. 3189-3205 ◽  
Author(s):  
Ashoka Chary Taviti ◽  
Tushar Kant Beuria
Keyword(s):  
Cell Division ◽  
Single Point ◽  
Point Mutations ◽  
Direct Interaction ◽  
Ring Formation ◽  
Z Ring ◽  
Single Point Mutations ◽  
Biochemical Analyses ◽  
Ftsz Assembly ◽  
The Mind

Cell division in bacteria is a highly controlled and regulated process. FtsZ, a bacterial cytoskeletal protein, forms a ring-like structure known as the Z-ring and recruits more than a dozen other cell division proteins. The Min system oscillates between the poles and inhibits the Z-ring formation at the poles by perturbing FtsZ assembly. This leads to an increase in the FtsZ concentration at the mid-cell and helps in Z-ring positioning. MinC, the effector protein, interferes with Z-ring formation through two different mechanisms mediated by its two domains with the help of MinD. However, the mechanism by which MinD triggers MinC activity is not yet known. We showed that MinD directly interacts with FtsZ with an affinity stronger than the reported MinC–FtsZ interaction. We determined the MinD-binding site of FtsZ using computational, mutational and biochemical analyses. Our study showed that MinD binds to the H10 helix of FtsZ. Single-point mutations at the charged residues in the H10 helix resulted in a decrease in the FtsZ affinity towards MinD. Based on our findings, we propose a novel model for MinCD–FtsZ interaction, where MinD through its direct interaction with FtsZ would trigger MinC activity to inhibit FtsZ functions.

scholarly journals Genetic diversity of the Neotropical otter (Lontra longicaudis Olfers, 1818) in Southern and Southeastern Brazil

2007 ◽  
Vol 67 (4 suppl) ◽  
pp. 813-818 ◽  
Author(s):  
CS. Trinca ◽  
HF. Waldemarin ◽  
E. Eizirik
Keyword(s):  
Molecular Diversity ◽  
Single Point ◽  
Haplotype Diversity ◽  
Point Mutations ◽  
Conservation Strategies ◽  
Southeastern Brazil ◽  
Nucleotide Variability ◽  
Single Point Mutations ◽  
High Level ◽  
Lontra Longicaudis

The Neotropical otter is one of the least known otter species, and it is considered to be threatened to various degrees throughout its geographic range. Little information exists on the ecological characteristics of this species, and no genetic study has been published about it until now, hampering the design of adequate conservation strategies for its populations. To contribute with genetic information to comprehensive conservation efforts on behalf of L. longicaudis, we characterized the molecular diversity of the 5’ portion of the mtDNA control region in samples from this species collected in Southern and Southeastern Brazil. The sequence analysis revealed a high level of haplotype diversity (h = 0.819; SE = 0.0052) and nucleotide variability ranging from 0.0039 to 0.0067. One of the sampled haplotypes was the most common in both regions and, from this sequence, several other (locally occurring) haplotypes could be derived by single point mutations. No significant genetic differentiation was observed between the Southern and Southeastern regions.

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