scholarly journals Methyltransferase as Antibiotics Against Foodborne Pathogens: An In Silico Approach for Exploring Enzyme as Enzymobiotics

2022 ◽  
Vol 12 ◽  
Author(s):  
Varish Ahmad ◽  
Aftab Ahmad ◽  
Mohammed F. Abuzinadah ◽  
Salwa Al-Thawdi ◽  
Ghazala Yunus
Keyword(s):  
Protein Interactions ◽  
Foodborne Pathogens ◽  
In Silico ◽  
Foodborne Pathogen ◽  
Cellular Protein ◽  
Protein Protein Interactions ◽  
Protein Requirements ◽  
Development Of Resistance ◽  
Enzyme Sequence ◽  
Limited Choice

The development of resistance in microbes against antibiotics and limited choice for the use of chemical preservatives in food lead the urgent need to search for an alternative to antibiotics. The enzymes are catalytic proteins that catalyze digestion of bacterial cell walls and protein requirements for the survival of the cell. To study methyltransferase as antibiotics against foodborne pathogen, the methyltransferase enzyme sequence was modeled and its interactions were analyzed against a membrane protein of the gram-positive and gram-negative bacteria through in silico protein–protein interactions. The methyltransferase interaction with cellular protein was found to be maximum, due to the maximum PatchDock Score (15808), which was followed by colicin (12864) and amoxicillin (4122). The modeled protein has found to be interact more significantly to inhibit the indicator bacteria than the tested antibiotics and antimicrobial colicin protein. Thus, model enzyme methyltransferase could be used as enzymobiotics. Moreover, peptide sequences similar to this enzyme sequence need to be designed and evaluated against the microbial pathogen.

Aryloxy Triester Phosphoramidates as Phosphoserine Biocleavable Masking Motifs

2019 ◽  
Author(s):  
Ageo Miccoli ◽  
Binar A. Dhiani ◽  
Peter J. Thornton ◽  
Olivia A. Lambourne ◽  
Edward James ◽  
...  
Keyword(s):  
Small Molecules ◽  
Protein Interactions ◽  
In Silico ◽  
Parent Compound ◽  
Cellular Protein ◽  
Carboxypeptidase Y ◽  
Protein Protein Interactions ◽  
Enzymatic Assays ◽  
Specific Targeting

Many cellular protein-protein interactions (PPIs) are mediated by phosphoserine. The specific targeting of these PPIs by phosphoserine-containing small molecules has been scarce due to the dephosphorylation of phosphoserine and its charged nature at physiological pH, which hinders its uptake into cells. To address these issues, we herein report the masking of the phosphate group of phosphoserine with biocleavable aryloxy triester phosphoramidate groups. A combination of <i>in vitro</i> enzymatic assays and <i>in silico</i> studies, using carboxypeptidase Y and Hint-1 respectively, showed that the phosphate masking groups are metabolized to release phosphoserine. To probe the applicability of this phosphoserine masking approach, it was applied to a phosphoserine-containing inhibitor of 14-3-3 dimerization, and this generated molecules with improved pharmacological activity in cells compared to their unmasked phosphoserine-containing parent compound. Collectively, the data showcases the masking of phosphoserine with biocleavable aryloxy triester phosphoramidate masking groups as an efficient intracellular delivery system for phosphoserine-containing molecules.

Aryloxy Triester Phosphoramidates as Phosphoserine Biocleavable Masking Motifs

2019 ◽  
Author(s):  
Ageo Miccoli ◽  
Binar A. Dhiani ◽  
Peter J. Thornton ◽  
Olivia A. Lambourne ◽  
Edward James ◽  
...  
Keyword(s):  
Small Molecules ◽  
Protein Interactions ◽  
In Silico ◽  
Parent Compound ◽  
Cellular Protein ◽  
Carboxypeptidase Y ◽  
Protein Protein Interactions ◽  
Enzymatic Assays ◽  
Specific Targeting

Many cellular protein-protein interactions (PPIs) are mediated by phosphoserine. The specific targeting of these PPIs by phosphoserine-containing small molecules has been scarce due to the dephosphorylation of phosphoserine and its charged nature at physiological pH, which hinders its uptake into cells. To address these issues, we herein report the masking of the phosphate group of phosphoserine with biocleavable aryloxy triester phosphoramidate groups. A combination of <i>in vitro</i> enzymatic assays and <i>in silico</i> studies, using carboxypeptidase Y and Hint-1 respectively, showed that the phosphate masking groups are metabolized to release phosphoserine. To probe the applicability of this phosphoserine masking approach, it was applied to a phosphoserine-containing inhibitor of 14-3-3 dimerization, and this generated molecules with improved pharmacological activity in cells compared to their unmasked phosphoserine-containing parent compound. Collectively, the data showcases the masking of phosphoserine with biocleavable aryloxy triester phosphoramidate masking groups as an efficient intracellular delivery system for phosphoserine-containing molecules.

scholarly journals Exploring Protein-Protein Interactions as Drug Targets for Anti-cancer Therapy with In Silico Workflows

2017 ◽  
pp. 221-236 ◽  
Author(s):  
Alexander Goncearenco ◽  
Minghui Li ◽  
Franco L. Simonetti ◽  
Benjamin A. Shoemaker ◽  
Anna R. Panchenko
Keyword(s):  
Cancer Therapy ◽  
Protein Interactions ◽  
In Silico ◽  
Drug Targets ◽  
Protein Protein Interactions ◽  
Anti Cancer

scholarly journals In Silico and In Vitro Studies on the Protein-Protein Interactions between Brugia malayi Immunomodulatory Protein Calreticulin and Human C1q

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e106413 ◽  
Author(s):  
Sunita Yadav ◽  
Smita Gupta ◽  
Chandrabose Selvaraj ◽  
Pawan Kumar Doharey ◽  
Anita Verma ◽  
...  
Keyword(s):  
Protein Interactions ◽  
In Silico ◽  
Brugia Malayi ◽  
In Vitro Studies ◽  
Protein Protein Interactions ◽  
Immunomodulatory Protein

scholarly journals Molecular dynamics shows complex interplay and long-range effects of post-translational modifications in yeast protein interactions

2021 ◽  
Vol 17 (5) ◽  
pp. e1008988
Author(s):  
Nikolina ŠoŠtarić ◽  
Vera van Noort
Keyword(s):  
Molecular Dynamics ◽  
Conformational Changes ◽  
Protein Interactions ◽  
Protein Structures ◽  
Cellular Protein ◽  
Free Energy Calculations ◽  
Protein Protein Interactions ◽  
Post Translational Modifications ◽  
Protein Properties ◽  
Dynamics Simulations

Post-translational modifications (PTMs) play a vital, yet often overlooked role in the living cells through modulation of protein properties, such as localization and affinity towards their interactors, thereby enabling quick adaptation to changing environmental conditions. We have previously benchmarked a computational framework for the prediction of PTMs’ effects on the stability of protein-protein interactions, which has molecular dynamics simulations followed by free energy calculations at its core. In the present work, we apply this framework to publicly available data on Saccharomyces cerevisiae protein structures and PTM sites, identified in both normal and stress conditions. We predict proteome-wide effects of acetylations and phosphorylations on protein-protein interactions and find that acetylations more frequently have locally stabilizing roles in protein interactions, while the opposite is true for phosphorylations. However, the overall impact of PTMs on protein-protein interactions is more complex than a simple sum of local changes caused by the introduction of PTMs and adds to our understanding of PTM cross-talk. We further use the obtained data to calculate the conformational changes brought about by PTMs. Finally, conservation of the analyzed PTM residues in orthologues shows that some predictions for yeast proteins will be mirrored to other organisms, including human. This work, therefore, contributes to our overall understanding of the modulation of the cellular protein interaction networks in yeast and beyond.

scholarly journals Structural Model of the hUbA1-UbcH10 Quaternary Complex: In Silico and Experimental Analysis of the Protein-Protein Interactions between E1, E2 and Ubiquitin

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e112082 ◽  
Author(s):  
Stefania Correale ◽  
Ivan de Paola ◽  
Carmine Marco Morgillo ◽  
Antonella Federico ◽  
Laura Zaccaro ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Experimental Analysis ◽  
In Silico ◽  
Structural Model ◽  
Protein Protein Interactions ◽  
Quaternary Complex

Chapter 1. Identification of Cellular Protein–Protein Interactions

2020 ◽  
pp. 1-39
Author(s):  
Caroline Benz ◽  
Eszter Kassa ◽  
Elias Tjärnhage ◽  
Sara Bergström Lind ◽  
Ylva Ivarsson
Keyword(s):  
Protein Interactions ◽  
Cellular Protein ◽  
Protein Protein Interactions

Protein-Protein Interactions (PPIs) as an Alternative to Targeting the ATP Binding Site of Kinase

2016 ◽  
pp. 249-277
Author(s):  
Sailu Sarvagalla ◽  
Mohane Selvaraj Coumar
Keyword(s):  
Protein Interactions ◽  
In Silico ◽  
Rational Design ◽  
Kinase Activity ◽  
Hot Spot ◽  
Binding Pocket ◽  
Atp Binding ◽  
Protein Protein Interactions ◽  
Structure Based Drug Design ◽  
Atp Binding Site

Most of the developed kinase inhibitor drugs are ATP competitive and suffer from drawbacks such as off-target kinase activity, development of resistance due to mutation in the ATP binding pocket and unfavorable intellectual property situations. Besides the ATP binding pocket, protein kinases have binding sites that are involved in Protein-Protein Interactions (PPIs); these PPIs directly or indirectly regulate the protein kinase activity. Of recent, small molecule inhibitors of PPIs are emerging as an alternative to ATP competitive agents. Rational design of inhibitors for kinase PPIs could be carried out using molecular modeling techniques. In silico tools available for the prediction of hot spot residues and cavities at the PPI sites and the means to utilize this information for the identification of inhibitors are discussed. Moreover, in silico studies to target the Aurora B-INCENP PPI sites are discussed in context. Overall, this chapter provides detailed in silico strategies that are available to the researchers for carrying out structure-based drug design of PPI inhibitors.

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