Structural Basis for the Mutation-Induced Dysfunction of Human CYP2J2: A Computational Study

2013 ◽  
Vol 53 (6) ◽  
pp. 1350-1357 ◽  
Author(s):  
Shan Cong ◽  
Xiao-Tu Ma ◽  
Yi-Xue Li ◽  
Jing-Fang Wang
Keyword(s):  
Computational Study ◽  
Structural Basis

scholarly journals Correction: Dynamic properties of dipeptidyl peptidase III from Bacteroides thetaiotaomicron and the structural basis for its substrate specificity – a computational study

2017 ◽  
Vol 13 (12) ◽  
pp. 2729-2730
Author(s):  
M. Tomin ◽  
S. Tomić
Keyword(s):  
Substrate Specificity ◽  
Computational Study ◽  
Dynamic Properties ◽  
Dipeptidyl Peptidase ◽  
Structural Basis ◽  
Bacteroides Thetaiotaomicron

Correction for ‘Dynamic properties of dipeptidyl peptidase III from Bacteroides thetaiotaomicron and the structural basis for its substrate specificity – a computational study’ by M. Tomin et al., Mol. BioSyst., 2017, 13, 2407–2417.

scholarly journals Dynamic properties of dipeptidyl peptidase III from Bacteroides thetaiotaomicron and the structural basis for its substrate specificity – a computational study

2017 ◽  
Vol 13 (11) ◽  
pp. 2407-2417 ◽  
Author(s):  
M. Tomin ◽  
S. Tomić
Keyword(s):  
Enzyme Activity ◽  
Substrate Specificity ◽  
Computational Study ◽  
Dynamic Properties ◽  
Dipeptidyl Peptidase ◽  
Structural Basis ◽  
Wild Type ◽  
Bacteroides Thetaiotaomicron ◽  
Human Gut

Dynamics and enzyme activity of dipeptidyl peptidase III, wild type and mutants, from the human gut symbiont Bacteroides thetaiotaomicron.

Computational Analysis of Dipyrone Metabolite 4-Aminoantipyrine As A Cannabinoid Receptor 1 Agonist

2020 ◽  
Vol 27 (28) ◽  
pp. 4741-4749 ◽  
Author(s):  
Silvana Russo ◽  
Walter Filgueira de Azevedo
Keyword(s):  
Cannabinoid Receptor ◽  
Computational Study ◽  
Structural Basis ◽  
Crystallographic Structure ◽  
Cannabinoid Receptor 1 ◽  
Docking Simulations ◽  
Functional Studies ◽  
Protein Ligand Interactions ◽  
Mechanistic Analysis ◽  
Ligand Interactions

Background: Cannabinoid receptor 1 has its crystallographic structure available in complex with agonists and inverse agonists, which paved the way to establish an understanding of the structural basis of interactions with ligands. Dipyrone is a prodrug with analgesic capabilities and is widely used in some countries. Recently some evidence of a dipyrone metabolite acting over the Cannabinoid Receptor 1has been shown. Objective: Our goal here is to explore the dipyrone metabolite 4-aminoantipyrine as a Cannabinoid Receptor 1 agonist, reviewing dipyrone characteristics, and investigating the structural basis for its interaction with the Cannabinoid Receptor 1. Method: We reviewed here recent functional studies related to the dipyrone metabolite focusing on its action as a Cannabinoid Receptor 1 agonist. We also analyzed protein-ligand interactions for this complex obtained through docking simulations against the crystallographic structure of the Cannabinoid Receptor 1. Results: Analysis of the crystallographic structure and docking simulations revealed that most of the interactions present in the docked pose were also present in the crystallographic structure of Cannabinoid Receptor 1 and agonist. Conclusion: Analysis of the complex of 4-aminoantipyrine and Cannabinoid Receptor 1 revealed the pivotal role played by residues Phe 170, Phe 174, Phe 177, Phe 189, Leu 193, Val 196, and Phe 379, besides the conserved hydrogen bond at Ser 383. The mechanistic analysis and the present computational study suggest that the dipyrone metabolite 4-aminoantipyrine interacts with the Cannabinoid Receptor 1.

scholarly journals Structural Basis for Amyloid β-Protein Toxicity Inhibition: A Multiscale Computational Study

2011 ◽  
Vol 100 (3) ◽  
pp. 390a
Author(s):  
Brigita Urbanc ◽  
Bogdan Barz ◽  
Mark Betnel ◽  
Luis Cruz ◽  
Gal Bitan ◽  
...  
Keyword(s):  
Computational Study ◽  
Amyloid Β ◽  
Structural Basis ◽  
Amyloid Β Protein ◽  
Β Protein ◽  
Protein Toxicity

scholarly journals A comprehensive evaluation of the potential binding poses of fentanyl and its analogs at the µ-opioid receptor

2021 ◽  
Author(s):  
Bing Xie ◽  
Alexander Goldberg ◽  
Lei Shi
Keyword(s):  
Opioid Receptor ◽  
Comprehensive Evaluation ◽  
Computational Study ◽  
Energy Landscape ◽  
Drug Market ◽  
Binding Pocket ◽  
Structural Basis ◽  
Binding Mechanism ◽  
Fentanyl Analogs ◽  
Dynamics Simulations

Fentanyl and its analogs are selective agonists of the µ-opioid receptor (MOR). Among novel synthetic opioids (NSOs), they dominate the recreational drug market and are the main culprits for the opioid crisis, which has been exacerbated by the COVID-19 pandemic. By taking advantage of the crystal structures of the MOR, several groups have investigated the binding mechanism of fentanyl, but have not reached a consensus, in terms of both the binding orientation and the fentanyl conformation. Thus, the binding mechanism of fentanyl at the MOR remains an unsolved and challenging question. Here, we carried out a systematic computational study to investigate the preferred fentanyl conformations, and how these conformations are being accommodated in the MOR binding pocket. We characterized the free energy landscape of fentanyl conformations with metadynamics simulations, as well as performed long-timescale molecular dynamics simulations to compare and evaluate several possible fentanyl binding conditions. Our results indicate that the most preferred binding pose in the MOR binding pocket corresponds well with the minima on the energy landscape of fentanyl in the absence of the receptor, while the energy landscape can be reconfigured by modifying the fentanyl scaffold. The interactions with the receptor may stabilize a slightly unfavored fentanyl conformation in an alternative binding pose. By extending similar investigations to fentanyl analogs, our findings establish a structure-activity relationship of fentanyl binding at the MOR. In addition to providing a structural basis to understand the potential toxicity of the emerging NSOs, such insights will contribute to developing new, safer analgesics.

scholarly journals Computational Study of Ions and Water Permeation and Transportation Mechanisms of the SARS-CoV-2 Pentameric E Protein Channel

2020 ◽  
Author(s):  
Yipeng Cao ◽  
Rui Yang ◽  
Wei Wang ◽  
Imshik Lee ◽  
Ruiping Zhang ◽  
...  
Keyword(s):  
Computational Study ◽  
Monovalent Cation ◽  
Structural Basis ◽  
Hydrophobic Membrane ◽  
Water Permeation ◽  
Cation Selectivity ◽  
E Protein ◽  
Monovalent Ions ◽  
Protein Channel ◽  
Novel Coronavirus

AbstractCoronavirus disease 2019 (COVID-19) is caused by a novel coronavirus (SARS-CoV-2) and represents the causative agent of a potentially fatal disease that is of public health emergency of international concern. Coronaviruses, including SARS-CoV-2, encode an envelope (E) protein, which is a small, hydrophobic membrane protein; the E protein of SARS-CoV-2 has high homology with that of severe acute respiratory syndrome coronavirus. (SARS-CoV) In this study, we provide insights into the function of the SARS-CoV-2 E protein channel and the ion and water permeation mechanisms on the basis of combined in silico methods. Our results suggest that the pentameric E protein promotes the penetration of monovalent ions through the channel. Analysis of the potential mean force (PMF), pore radius and diffusion coefficient reveals that Leu10 and Phe19 are the hydrophobic gates of the channel. In addition, the pore demonstrated a clear wetting/dewetting transition with monovalent cation selectivity under transmembrane voltage, which indicates that it is a hydrophobic voltage-dependent channel. Overall, these results provide structural-basis insights and molecular-dynamic information that are needed to understand the regulatory mechanisms of ion permeability in the pentameric SARS-CoV-2 E protein channel.

Organization of tight junctions in the choroid plexus epithelium

1978 ◽  
Vol 36 (2) ◽  
pp. 336-337
Author(s):  
B. Van Deurs ◽  
J. K. Koehler
Keyword(s):  
Choroid Plexus ◽  
Present Report ◽  
Freeze Fracture ◽  
Barrier Properties ◽  
Cell Junctions ◽  
Structural Basis ◽  
Apical Surface ◽  
Choroid Plexus Epithelium ◽  
Solid Nitrogen ◽  
Special Composition

The choroid plexus epithelium constitutes a blood-cerebrospinal fluid (CSF) barrier, and is involved in regulation of the special composition of the CSF. The epithelium is provided with an ouabain-sensitive Na/K-pump located at the apical surface, actively pumping ions into the CSF. The choroid plexus epithelium has been described as “leaky” with a low transepithelial resistance, and a passive transepithelial flux following a paracellular route (intercellular spaces and cell junctions) also takes place. The present report describes the structural basis for these “barrier” properties of the choroid plexus epithelium as revealed by freeze fracture.Choroid plexus from the lateral, third and fourth ventricles of rats were used. The tissue was fixed in glutaraldehyde and stored in 30% glycerol. Freezing was performed either in liquid nitrogen-cooled Freon 22, or directly in a mixture of liquid and solid nitrogen prepared in a special vacuum chamber. The latter method was always used, and considered necessary, when preparations of complementary (double) replicas were made.

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