scholarly journals Protein Residues That Control the Reaction Trajectory inS-Adenosylmethionine Radical Enzymes: Mutagenesis of Asparagine 153 and Aspartate 155 inEscherichia coliBiotin Synthase†

Biochemistry ◽  
2009 ◽  
Vol 48 (11) ◽  
pp. 2448-2458 ◽  
Author(s):  
Christine E. Farrar ◽  
Joseph T. Jarrett
Keyword(s):  
Protein Residues ◽  
Radical Enzymes

scholarly journals Computational Modeling to Explain Why 5,5-Diarylpentadienamides are TRPV1 Antagonists

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1765
Author(s):  
Julio Caballero
Keyword(s):  
Transient Receptor Potential ◽  
Structural Information ◽  
Chemical Activation ◽  
Receptor Potential ◽  
Quantitative Structure Activity Relationship ◽  
Structural Features ◽  
Transient Receptor Potential Vanilloid ◽  
Protein Residues ◽  
Topological Features ◽  
Transient Receptor

Several years ago, the crystallographic structures of the transient receptor potential vanilloid 1 (TRPV1) in the presence of agonists and antagonists were reported, providing structural information about its chemical activation and inactivation. TRPV1’s activation increases the transport of calcium and sodium ions, leading to the excitation of sensory neurons and the perception of pain. On the other hand, its antagonistic inactivation has been explored to design analgesic drugs. The interactions between the antagonists 5,5-diarylpentadienamides (DPDAs) and TRPV1 were studied here to explain why they inactivate TRPV1. The present work identified the structural features of TRPV1–DPDA complexes, starting with a consideration of the orientations of the ligands inside the TRPV1 binding site by using molecular docking. After this, a chemometrics analysis was performed (i) to compare the orientations of the antagonists (by using LigRMSD), (ii) to describe the recurrent interactions between the protein residues and ligand groups in the complexes (by using interaction fingerprints), and (iii) to describe the relationship between topological features of the ligands and their differential antagonistic activities (by using a quantitative structure–activity relationship (QSAR) with 2D autocorrelation descriptors). The interactions between the DPDA groups and the residues Y511, S512, T550, R557, and E570 (with a recognized role in the binding of classic ligands), and the occupancy of isoquinoline or 3-hydroxy-3,4-dihydroquinolin-2(1H)-one groups of the DPDAs in the vanilloid pocket of TRPV1 were clearly described. Based on the results, the structural features that explain why DPDAs inactivate TRPV1 were clearly exposed. These features can be considered for the design of novel TRPV1 antagonists.

scholarly journals Oxidative Modification of Native Protein Residues Using Cerium(IV) Ammonium Nitrate

2011 ◽  
Vol 133 (42) ◽  
pp. 16970-16976 ◽  
Author(s):  
Kristen L. Seim ◽  
Allie C. Obermeyer ◽  
Matthew B. Francis
Keyword(s):  
Ammonium Nitrate ◽  
Oxidative Modification ◽  
Native Protein ◽  
Protein Residues ◽  
Cerium Iv Ammonium Nitrate

scholarly journals Alphavirus Virulence Determinants

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 981
Author(s):  
Margarita V. Rangel ◽  
Kenneth A. Stapleford
Keyword(s):  
Viral Infections ◽  
Specific Protein ◽  
Chronic Arthritis ◽  
Virulence Determinants ◽  
Genetic Determinants ◽  
Protein Residues ◽  
Molecular Determinants ◽  
Public Health Threat ◽  
Significant Public Health ◽  
New Strategies

Alphaviruses are important pathogens that continue to cause outbreaks of disease in humans and animals worldwide. Diseases caused by alphavirus infections include acute symptoms of fever, rash, and nausea as well as chronic arthritis and severe-to-fatal conditions including myocarditis and encephalitis. Despite their prevalence and the significant public health threat they pose, there are currently no effective antiviral treatments or vaccines against alphaviruses. Various genetic determinants of alphavirus virulence, including genomic RNA elements and specific protein residues and domains, have been described by researchers to play key roles in the development of disease, the immune response to infection, and virus transmissibility. Here, we focus on the determinants that are currently described in the literature. Understanding how these molecular determinants shape viral infections can lead to new strategies for the development of therapies and vaccines to combat these viruses.

scholarly journals Co-Evolution of Intrinsically Disordered Proteins with Folded Partners Witnessed by Evolutionary Couplings

2018 ◽  
Vol 19 (11) ◽  
pp. 3315 ◽  
Author(s):  
Rita Pancsa ◽  
Fruzsina Zsolyomi ◽  
Peter Tompa
Keyword(s):  
Large Scale ◽  
Intrinsically Disordered Proteins ◽  
Protein Structures ◽  
Disordered Proteins ◽  
Cellular Interaction ◽  
Structural Constraints ◽  
Protein Residues ◽  
Intrinsically Disordered ◽  
Evolutionary Changes ◽  
Folded Proteins

Although improved strategies for the detection and analysis of evolutionary couplings (ECs) between protein residues already enable the prediction of protein structures and interactions, they are mostly restricted to conserved and well-folded proteins. Whereas intrinsically disordered proteins (IDPs) are central to cellular interaction networks, due to the lack of strict structural constraints, they undergo faster evolutionary changes than folded domains. This makes the reliable identification and alignment of IDP homologs difficult, which led to IDPs being omitted in most large-scale residue co-variation analyses. By preforming a dedicated analysis of phylogenetically widespread bacterial IDP–partner interactions, here we demonstrate that partner binding imposes constraints on IDP sequences that manifest in detectable interprotein ECs. These ECs were not detected for interactions mediated by short motifs, rather for those with larger IDP–partner interfaces. Most identified coupled residue pairs reside close (<10 Å) to each other on the interface, with a third of them forming multiple direct atomic contacts. EC-carrying interfaces of IDPs are enriched in negatively charged residues, and the EC residues of both IDPs and partners preferentially reside in helices. Our analysis brings hope that IDP–partner interactions difficult to study could soon be successfully dissected through residue co-variation analysis.

De Novo Proteins as Models of Radical Enzymes†

Biochemistry ◽  
1999 ◽  
Vol 38 (29) ◽  
pp. 9495-9507 ◽  
Author(s):  
Cecilia Tommos ◽  
Jack J. Skalicky ◽  
Denis L. Pilloud ◽  
A. Joshua Wand ◽  
P. Leslie Dutton
Keyword(s):  
De Novo ◽  
De Novo Proteins ◽  
Radical Enzymes
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