Faculty Opinions recommendation of The use of orthologous sequences to predict the impact of amino acid substitutions on protein function.

2010 ◽  
Author(s):  
Alejandro Schaffer
Keyword(s):  
Amino Acid ◽  
Protein Function ◽  
Amino Acid Substitutions ◽  
The Impact

scholarly journals The Use of Orthologous Sequences to Predict the Impact of Amino Acid Substitutions on Protein Function

PLoS Genetics ◽  
2010 ◽  
Vol 6 (5) ◽  
pp. e1000968 ◽  
Author(s):  
Nicholas J. Marini ◽  
Paul D. Thomas ◽  
Jasper Rine
Keyword(s):  
Amino Acid ◽  
Protein Function ◽  
Amino Acid Substitutions ◽  
The Impact

scholarly journals Epistatic interactions can moderate the antigenic effect of substitutions in hemagglutinin of influenza H3N2 virus

2018 ◽  
Author(s):  
Björn F. Koel ◽  
David F. Burke ◽  
Stefan van der Vliet ◽  
Theo M. Bestebroer ◽  
Guus F. Rimmelzwaan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Context Dependence ◽  
Single Amino Acid ◽  
H3n2 Virus ◽  
Amino Acid Substitutions ◽  
Epistatic Interactions ◽  
Context Dependent ◽  
The Impact ◽  
Influenza H3n2

AbstractWe previously showed that single amino acid substitutions at seven positions in hemagglutinin determined major antigenic change of influenza H3N2 virus. Here, the impact of two such substitutions was tested in eleven representative H3 hemagglutinins to investigate context-dependence effects. The antigenic effect of substitutions introduced at hemagglutinin position 145 was fully independent of the amino acid context of the representative hemagglutinins. Antigenic change caused by substitutions introduced at hemagglutinin position 155 was variable and context-dependent. Our results suggest that epistatic interactions with contextual amino acids in the hemagglutinin can moderate the magnitude of antigenic change.

scholarly journals Adaptive amino acid substitutions enable transmission of an H9N2 avian influenza virus in guinea pigs

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Liu Lina ◽  
Chen Saijuan ◽  
Wang Chengyu ◽  
Lu Yuefeng ◽  
Dong Shishan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Hong Kong ◽  
Amino Acid ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Reverse Genetics ◽  
Amino Acid Substitutions ◽  
Potential Threat ◽  
Pathogenic Avian Influenza Virus ◽  
The Impact

AbstractH9N2 is the most prevalent low pathogenic avian influenza virus (LPAIV) in domestic poultry in the world. Two distinct H9N2 poultry lineages, G1-like (A/quail/Hong Kong/G1/97) and Y280-like (A/Duck/Hong Kong/Y280/1997) viruses, are usually associated with binding affinity for both α 2,3 and α 2,6 sialic acid receptors (avian and human receptors), raising concern whether these viruses possess pandemic potential. To explore the impact of mouse adaptation on the transmissibility of a Y280-like virus A/Chicken/Hubei/214/2017(H9N2) (abbreviated as WT), we performed serial lung-to-lung passages of the WT virus in mice. The mouse-adapted variant (MA) exhibited enhanced pathogenicity and advantaged transmissibility after passaging in mice. Sequence analysis of the complete genomes of the MA virus revealed a total of 16 amino acid substitutions. These mutations distributed across 7 segments including PB2, PB1, PA, NP, HA, NA and NS1 genes. Furthermore, we generated a panel of recombinant or mutant H9N2 viruses using reverse genetics technology and confirmed that the PB2 gene governing the increased pathogenicity and transmissibility. The combinations of 340 K and 588 V in PB2 were important in determining the altered features. Our findings elucidate the specific mutations in PB2 contribute to the phenotype differences and emphasize the importance of monitoring the identified amino acid substitutions due to their potential threat to human health.

scholarly journals Analysis of Large-Scale Mutagenesis Data To Assess the Impact of Single Amino Acid Substitutions

Genetics ◽  
2017 ◽  
Vol 207 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Vanessa E. Gray ◽  
Ronald J. Hause ◽  
Douglas M. Fowler
Keyword(s):  
Amino Acid ◽  
Large Scale ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
The Impact

scholarly journals Impact of Amino Acid Substitutions in Region II and Helix K of HSV-1 and HCMV DNA Polymerases on Resistance to Foscarnet

2021 ◽  
Author(s):  
Karima Zarrouk ◽  
Xiaojun Zhu ◽  
Van Dung Pham ◽  
Nathalie Goyette ◽  
Jocelyne Piret ◽  
...  
Keyword(s):  
Amino Acid ◽  
Conformational Changes ◽  
Recombinant Dna ◽  
Three Dimensional ◽  
Amino Acid Substitutions ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
The Impact ◽  
Region Ii ◽  
Hsv 1

Amino acid substitutions conferring resistance of herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) to foscarnet (PFA) are respectively located in UL30 and UL54 genes encoding the DNA polymerase (pol). In this study, we analyzed the impact of substitutions located in helix K and region II that are involved in the conformational changes of the DNA pol. Theoretical substitutions were identified by sequences alignment of the helix K and region II of human herpesviruses (susceptible to PFA) and bacteriophages (resistant to PFA) and introduced in viral genomes by recombinant phenotyping. We characterized the susceptibility of HSV-1 and HCMV mutants to PFA. In UL30, substitutions I619K (helix K), V715S and A719T (both in region II) increased mean PFA EC50 by 2.5-, 5.6- and 2.0-fold compared to wild type (WT), respectively. In UL54, substitution Q579I (helix K) conferred hypersusceptibility to PFA (0.17-fold change) whereas substitutions Q697P, V715S and A719T (all in region II) increased mean PFA EC50 values by 3.8-, 2.8- and 2.5-fold compared to WT, respectively. These results were confirmed by enzymatic assays using recombinant DNA pol harboring these substitutions. Three-dimensional modeling suggests that substitutions conferring resistance/hypersusceptibility to PFA located in helix K and region II of UL30 and UL54 DNA pol favor an open/closed conformation of these enzymes resulting in a lower/higher drug affinity for the proteins. Thus, this study shows that both regions of UL30 and UL54 DNA pol are involved in the conformational changes of these proteins and can influence the susceptibility of both viruses to PFA.

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