scholarly journals In Silico Predictions of Ecological Plasticity Mediated by Protein Family Expansions in Early-Diverging Fungi

2022 ◽  
Vol 8 (1) ◽  
pp. 67
Author(s):  
Małgorzata Orłowska ◽  
Anna Muszewska
Keyword(s):  
In Silico ◽  
Experimental Validation ◽  
Protein Family ◽  
Fungal Ecology ◽  
Protein Families ◽  
Carbohydrate Active Enzymes ◽  
Ecological Features ◽  
Multiple Protein ◽  
In Silico Predictions ◽  
First Time

Early-diverging fungi (EDF) are ubiquitous and versatile. Their diversity is reflected in their genome sizes and complexity. For instance, multiple protein families have been reported to expand or disappear either in particular genomes or even whole lineages. The most commonly mentioned are CAZymes (carbohydrate-active enzymes), peptidases and transporters that serve multiple biological roles connected to, e.g., metabolism and nutrients intake. In order to study the link between ecology and its genomic underpinnings in a more comprehensive manner, we carried out a systematic in silico survey of protein family expansions and losses among EDF with diverse lifestyles. We found that 86 protein families are represented differently according to EDF ecological features (assessed by median count differences). Among these there are 19 families of proteases, 43 CAZymes and 24 transporters. Some of these protein families have been recognized before as serine and metallopeptidases, cellulases and other nutrition-related enzymes. Other clearly pronounced differences refer to cell wall remodelling and glycosylation. We hypothesize that these protein families altogether define the preliminary fungal adaptasome. However, our findings need experimental validation. Many of the protein families have never been characterized in fungi and are discussed in the light of fungal ecology for the first time.

Metabolic Regio- and Stereoselectivity of Cytochrome P450 2D6 towards 3,4-Methylenedioxy-N-alkylamphetamines:  in Silico Predictions and Experimental Validation

2005 ◽  
Vol 48 (19) ◽  
pp. 6117-6127 ◽  
Author(s):  
Peter H. J. Keizers ◽  
Chris de Graaf ◽  
Frans J. J. de Kanter ◽  
Chris Oostenbrink ◽  
K. Anton Feenstra ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
In Silico ◽  
Experimental Validation ◽  
Cytochrome P450 2D6 ◽  
In Silico Predictions ◽  
P450 2D6

Metabolic stereoselectivity of cytochrome P450 3A4 towards deoxypodophyllotoxin: In silico predictions and experimental validation

2008 ◽  
Vol 43 (6) ◽  
pp. 1171-1179 ◽  
Author(s):  
Mattijs K. Julsing ◽  
Nikolay P. Vasilev ◽  
Dina Schneidman-Duhovny ◽  
Remco Muntendam ◽  
Herman J. Woerdenbag ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
In Silico ◽  
Experimental Validation ◽  
Cytochrome P450 3A4 ◽  
In Silico Predictions

scholarly journals Low-frequency variants at the CYP2C9 locus among Puerto Rican patients on warfarin: in silico predictions of functionality and conservation

2019 ◽  
Vol 20 (12) ◽  
pp. 891-902
Author(s):  
Karla Claudio-Campos ◽  
Mariangeli Moneró-Paredes ◽  
Eliud Hernández ◽  
Jessicca Renta ◽  
Jorge Duconge
Keyword(s):  
Conformational Changes ◽  
In Silico ◽  
Warfarin Therapy ◽  
African Ancestry ◽  
Low Frequency ◽  
Docking Analysis ◽  
Functional Consequences ◽  
In Silico Predictions ◽  
First Time ◽  
Generation Sequencing

Aim: Perform in silico predictions of functional consequences of CYP2C9 variants identified by next-generation sequencing in Puerto Ricans. Methods: Identified low-frequency CYP2C9 variants (minor allele frequencies <2%) were evaluated using the Combined Annotation-Dependent Depletion (CADD v1.3) tools and molecular modeling/docking analysis to predict impact on CYP2C9 activity. Results: CYP2C9*5, *8, *9, *11, *12,*21 and a novel *61 induce conformational changes that affect the binding site of S-warfarin. Most of these deleterious variants occur at higher frequency among individuals with large African ancestry. Conclusion: The unfavorable distance of S-warfarin from heme group, and low-binding interactions due to these CYP2C9 variants, suggest major complications during warfarin therapy. This study contributes to the field by predicting functional alterations of rare CYP2C9 variants for the first time in Hispanics.

3D mapping and in silico predictions of the DEHAL1 enzyme as a tool to discriminate pathogenic mutations from non-functional variants in hypothyroidism

2019 ◽  
Author(s):  
Garcia-Gimenez Jorge ◽  
Gonzalez Wong Angel ◽  
Gonzalez-Guerrero Cristian ◽  
Iglesias Ainhoa ◽  
Styrers Emily ◽  
...  
Keyword(s):  
In Silico ◽  
3D Mapping ◽  
Functional Variants ◽  
Pathogenic Mutations ◽  
In Silico Predictions

scholarly journals Identification of Potential HCV Inhibitors Based on the Interaction of Epigallocatechin-3-Gallate with Viral Envelope Proteins

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1257
Author(s):  
Fareena Shahid ◽  
Noreen ◽  
Roshan Ali ◽  
Syed Lal Badshah ◽  
Syed Babar Jamal ◽  
...  
Keyword(s):  
Hepatitis C ◽  
In Silico ◽  
Experimental Validation ◽  
Homology Modelling ◽  
Viral Envelope ◽  
Screening Methods ◽  
Binding Affinities ◽  
Autodock Vina ◽  
Potential Inhibitors ◽  
Very High

Hepatitis C is affecting millions of people around the globe annually, which leads to death in very high numbers. After many years of research, hepatitis C virus (HCV) remains a serious threat to the human population and needs proper management. The in silico approach in the drug discovery process is an efficient method in identifying inhibitors for various diseases. In our study, the interaction between Epigallocatechin-3-gallate, a component of green tea, and envelope glycoprotein E2 of HCV is evaluated. Epigallocatechin-3-gallate is the most promising polyphenol approved through cell culture analysis that can inhibit the entry of HCV. Therefore, various in silico techniques have been employed to find out other potential inhibitors that can behave as EGCG. Thus, the homology modelling of E2 protein was performed. The potential lead molecules were predicted using ligand-based as well as structure-based virtual screening methods. The compounds obtained were then screened through PyRx. The drugs obtained were ranked based on their binding affinities. Furthermore, the docking of the topmost drugs was performed by AutoDock Vina, while its 2D interactions were plotted in LigPlot+. The lead compound mms02387687 (2-[[5-[(4-ethylphenoxy) methyl]-4-prop-2-enyl-1,2,4-triazol-3-yl] sulfanyl]-N-[3(trifluoromethyl) phenyl] acetamide) was ranked on top, and we believe it can serve as a drug against HCV in the future, owing to experimental validation.

Hel-N1/Hel-N2 proteins are bound to poly(A)+ mRNA in granular RNP structures and are implicated in neuronal differentiation

1996 ◽  
Vol 109 (3) ◽  
pp. 579-589 ◽  
Author(s):  
F.B. Gao ◽  
J.D. Keene
Keyword(s):  
Neuronal Differentiation ◽  
Protein Family ◽  
Rna Recognition Motifs ◽  
Mrna Metabolism ◽  
Cell Extracts ◽  
Multiple Protein ◽  
Human Proteins ◽  
Mature Neurons ◽  
Recognition Motifs

Human proteins Hel-N1 and Hel-N2 contain three RNA recognition motifs (RRMs), and are members of a family of proteins highly homologous to Drosophila ELAV, which is essential for neuronal differentiation. Both proteins bind to A+U-rich 3′ untranslated regions of a variety of growth-related mRNAs in vitro. Here we demonstrate that in medulloblastoma cells derived from childhood brain tumors, Hel-N1 and Hel-N2 are mainly expressed in the cytoplasm, but are detectable in the nucleus. Both proteins are associated with polysomes and can be UV-crosslinked to poly(A)+ mRNA in cell extracts. In the cytoplasm the Hel-N1 protein family resides in granular structures that may contain multiple protein molecules bound to each mRNA. Evidence supporting this multimeric ribonucleoprotein (RNP) model includes in vitro reconstitution and competition experiments in which addition of a single RRM (RRM3) can alter complex formation. As in medulloblastoma cells, the Hel-N1 protein family is present in granular particles in the soma and the proximal regions of dendrites of cultured neurons, and colocalizes with ribosomes. In addition, we demonstrate that expression of the Hel-N1 protein family is up-regulated during neuronal differentiation of embryonic carcinoma P19 cells. Our data suggest that the Hel-N1 protein family is associated with the translational apparatus and implicated in both mRNA metabolism and neuronal differentiation. Furthermore, our findings open the possibility that these proteins participate in mRNA homeostasis in the dendrites and soma of mature neurons.

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