scholarly journals Unraveling the Molecular Mechanism of Recognition of Human Interferon-Stimulated Gene Product 15 by Coronavirus Papain-Like Proteases: A Multiscale Simulation Study

2021 ◽  
Author(s):  
Rajarshi Roy ◽  
Nisha Amarnath Jonniya ◽  
Sayan Poddar ◽  
Md Fulbabu Sk ◽  
Parimal Kar
Keyword(s):  
Gene Product ◽  
Molecular Mechanism ◽  
Simulation Study ◽  
Multiscale Simulation ◽  
Human Interferon ◽  
Mechanism Of Recognition

A multiscale simulation study of carbon nanotube interactions with designed amphiphilic peptide helices

Nanoscale ◽  
2010 ◽  
Vol 2 (6) ◽  
pp. 967 ◽  
Author(s):  
E. Jayne Wallace ◽  
Robert S. G. D'Rozario ◽  
Beatriz Mendoza Sanchez ◽  
Mark S. P. Sansom
Keyword(s):  
Carbon Nanotube ◽  
Simulation Study ◽  
Multiscale Simulation ◽  
Amphiphilic Peptide

scholarly journals Structurally Guided Removal of DeISGylase Biochemical Activity from Papain-Like Protease Originating from Middle East Respiratory Syndrome Coronavirus

2017 ◽  
Vol 91 (23) ◽  
Author(s):  
Courtney M. Daczkowski ◽  
Octavia Y. Goodwin ◽  
John V. Dzimianski ◽  
Jonathan J. Farhat ◽  
Scott D. Pegan
Keyword(s):  
Middle East ◽  
Gene Product ◽  
Isothermal Calorimetry ◽  
Middle East Respiratory Syndrome ◽  
Human Interferon ◽  
Type I ◽  
Peptide Cleavage ◽  
Terminal Domain ◽  
Immune Pathways ◽  
The Impact

ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging human pathogen that is the causative agent for Middle East respiratory syndrome (MERS). With MERS outbreaks resulting in over 35% fatalities and now spread to 27 countries, MERS-CoV poses a significant ongoing threat to global human health. As part of its viral genome, MERS-CoV encodes a papain-like protease (PLpro) that has been observed to act as a deubiquitinase and deISGylase to antagonize type I interferon (IFN-I) immune pathways. This activity is in addition to its viral polypeptide cleavage function. Although the overall impact of MERS-CoV PLpro function is observed to be essential, difficulty has been encountered in delineating the importance of its separate functions, particularly its deISGylase activity. As a result, the interface of MERS-CoV and human interferon-stimulated gene product 15 (hISG15) was probed with isothermal calorimetry, which suggests that the C-terminal domain of hISG15 is principally responsible for interactions. Subsequently, the structure of MERS-CoV PLpro was solved to 2.4 Å in complex with the C-terminal domain of hISG15. Utilizing this structural information, mutants were generated that lacked appreciable deISGylase activity but retained wild-type deubiquitinase and peptide cleavage activities. Hence, this provides a new platform for understanding viral deISGylase activity within MERS-CoV and other CoVs. IMPORTANCE Coronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV), encode a papain-like protease (PLpro) that possesses the ability to antagonize interferon immune pathways through the removal of ubiquitin and interferon-stimulated gene product 15 (ISG15) from target proteins. The lack of CoV proteases with attenuated deISGylase activity has been a key obstacle in delineating the impact between deubiquitinase and deISGylase activities on viral host evasion and pathogenesis. Here, biophysical techniques revealed that MERS-CoV PLpro chiefly engages human ISG15 through its C-terminal domain. The first structure of MERS-CoV PLpro in complex with this domain exposed the interface between these two entities. Employing these structural insights, mutations were employed to selectively remove deISGylase activity with no appreciable impact on its other deubiquitinase and peptide cleavage biochemical properties. Excitingly, this study introduces a new tool to probe the pathogenesis of MERS-CoV and related viruses through the removal of viral deISGylase activity.

Trace Benzene Separation from Vinyl Acetate: A Multiscale Simulation Study

2019 ◽  
Vol 58 (16) ◽  
pp. 6662-6669
Author(s):  
Xiuqin Dong ◽  
Wenzhe Hao ◽  
Zhongdong Gan ◽  
Yifei Chen ◽  
Minhua Zhang
Keyword(s):  
Vinyl Acetate ◽  
Simulation Study ◽  
Multiscale Simulation
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