scholarly journals Virtual Docking of VBP1 with HBX and NFκB Protein to Study the Activation of NFκB in the Regulatory Mechanism of Liver Cancer

2021 ◽  
pp. 21-28
Author(s):  
Mamta Sagar ◽  
Padma Saxena ◽  
Suruchi Singh ◽  
Ravindra Nath ◽  
Pramod W. Ramteke
Keyword(s):  
Amino Acids ◽  
Liver Cancer ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Von Hippel Lindau ◽  
Hbv Replication ◽  
Protein Ligand Interactions ◽  
B Virus ◽  
Ligand Interactions ◽  
The Common

Molecular docking is an efficient way to study protein-protein and protein-ligand interactions in virtual mode, this provides structural annotations of molecular interactions, required in the drug discovery process. The Cartesian FFT approach in ‘Hex’ spherical polar Fourier (SPF) uses rotational correlations, this method is used here to study protein-protein interactions. Hepatitis B virus (HBV) X protein (HBx) is essential for virus infection and has been used in the development of therapeutics for liver cancer. It can interact with many cellular proteins. It interferes with cell viability and stimulates HBV replication. The von Hippel-Lindau binding protein 1(VBP1) has an important role in HBx-mediated nuclear factor kappa B (NFkB) stimulation. VBP1 and HBx function as coactivators in the activation of NFκB binding. Docking results revealed that HBx and NFkB bind with VBP1 at the common site on amino acids positions Arg 161, Glu 92, and Arg 82, which may have a role in HBx-mediated NFκB activation. Lowest energy complex VBP1- NFkB1 was obtained at -883.70 Kcal/mol. The amino acids involved in interaction among HBx, VBP1, and NFκB proteins, may be involved in transcriptional regulation and has significance in normal and abnormal regulation. These amino acid interactions may be associated with the manifestation of Liver cancer.

scholarly journals Evolution of (p)ppGpp-HPRT regulation through diversification of an allosteric oligomeric interaction

2019 ◽  
Author(s):  
Brent W. Anderson ◽  
Kuanqing Liu ◽  
Christine Wolak ◽  
Katarzyna Dubiel ◽  
Kenneth A. Satyshur ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Binding Site ◽  
Protein Interactions ◽  
Binding Motif ◽  
Protein Ligand Interactions ◽  
Protein Interfaces ◽  
Ligand Interactions ◽  
Binding Residues ◽  
The Common ◽  
Ligand Regulation

ABSTRACTThe signaling ligand (p)ppGpp binds diverse targets across bacteria, yet the mechanistic and evolutionary basis underlying these ligand-protein interactions remains poorly understood. Here we identify a novel (p)ppGpp binding motif in the enzyme HPRT, where (p)ppGpp shares identical binding residues for PRPP and nucleobase substrates to regulate purine homeostasis. Intriguingly, HPRTs across species share the conserved binding site yet strongly differ in ligand binding, from strong inhibition by basal (p)ppGpp levels to weak regulation at induced concentrations. Surprisingly, strong ligand binding requires an HPRT dimer-dimer interaction that allosterically opens the (p)ppGpp pocket. This dimer-dimer interaction is absent in the common ancestor but evolved to favor (p)ppGpp binding in the vast majority of bacteria. We propose that the evolutionary plasticity of oligomeric interfaces enables allosteric adjustment of ligand regulation, bypassing constraints of the ligand binding site. Since most ligands bind near protein-protein interfaces, this principle likely extends to other protein-ligand interactions.

scholarly journals Uses of Phage Display in Agriculture: A Review of Food-Related Protein-Protein Interactions Discovered by Biopanning over Diverse Baits

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Rekha Kushwaha ◽  
Christina M. Payne ◽  
A. Bruce Downie
Keyword(s):  
Phage Display ◽  
Protein Interactions ◽  
Biofuel Production ◽  
Food Allergies ◽  
Protein Protein Interactions ◽  
Patient Response ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Repair Mechanisms ◽  
Complex Polymers

This review highlights discoveries made using phage display that impact the use of agricultural products. The contribution phage display made to our fundamental understanding of how various protective molecules serve to safeguard plants and seeds from herbivores and microbes is discussed. The utility of phage display for directed evolution of enzymes with enhanced capacities to degrade the complex polymers of the cell wall into molecules useful for biofuel production is surveyed. Food allergies are often directed against components of seeds; this review emphasizes how phage display has been employed to determine the seed component(s) contributing most to the allergenic reaction and how it has played a central role in novel approaches to mitigate patient response. Finally, an overview of the use of phage display in identifying the mature seed proteome protection and repair mechanisms is provided. The identification of specific classes of proteins preferentially bound by such protection and repair proteins leads to hypotheses concerning the importance of safeguarding the translational apparatus from damage during seed quiescence and environmental perturbations during germination. These examples, it is hoped, will spur the use of phage display in future plant science examining protein-ligand interactions.

Measures of cooperativity in the binding of ligands to proteins and their relation to non-additivity in protein-protein interactions

1986 ◽  
Vol 229 (1256) ◽  
pp. 315-329 ◽  
Keyword(s):  
Protein Interactions ◽  
Proteinase Inhibitors ◽  
Interaction Constant ◽  
Hill Coefficient ◽  
Protein Protein Interactions ◽  
Thermodynamic Cycles ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Hill Coefficients ◽  
The Hill

The analogy between cooperativity in the binding of ligands to proteins and non-additivity in protein-protein interactions is demonstrated and discussed in terms of the Wong and the Hill coefficients. A measure of non-additivity, the interaction constant , is rigorously derived for four thermodynamic cycles, involving the binding of small molecules to proteins and protein association. It is the reciprocal of the 1 defect factor of Laskowski et al. in Proteinase inhibitors: medical and biological aspects (ed. N. Katunuma et al.), pp. 55-68 (1983), andits logarithm is the Wong measure of cooperativity. These three measures are thus here given a common theoretical basis. The Hill coefficient for an asymmetric dimer that binds two different ligands which do not compete for the same site, at 50% saturation of each site, is derived. It is shown to be a function of the interaction constant and of the fraction of protein to which ligand is bound at both sites. These relations for protein-ligand interactions are then discussed in the context of non-additivity in protein-protein interactions.

scholarly journals Exploitation of proteomics strategies in protein structure-function studies

2003 ◽  
Vol 75 (2-3) ◽  
pp. 309-316 ◽  
Author(s):  
Gennaro Marino ◽  
P. Pucci ◽  
Leila Birolo ◽  
M. Ruoppolo
Keyword(s):  
Protein Interactions ◽  
Review Paper ◽  
Structural Proteomics ◽  
Protein Protein Interactions ◽  
Dna Interactions ◽  
Structural Genomic ◽  
Folding Intermediates ◽  
Protein Ligand Interactions ◽  
Protein Dna Interactions ◽  
Ligand Interactions

Mass spectrometry plays a central role in structural proteomics, particularly in highly intensive structural genomics projects. This review paper reports some examples taken from recent work from the authors' laboratory and is aimed at showing that modern proteomics strategies are instrumental in the integration of structural genomic projects in fields such as: (i) protein–protein interactions, (ii) protein-DNA interactions, (iii) protein–ligand interactions, and (iv) protein-folding intermediates.

scholarly journals 19F NMR as a tool in chemical biology

2021 ◽  
Vol 17 ◽  
pp. 293-318
Author(s):  
Diana Gimenez ◽  
Aoife Phelan ◽  
Cormac D Murphy ◽  
Steven L Cobb
Keyword(s):  
Structural Analysis ◽  
Nucleic Acids ◽  
Organic Compounds ◽  
Protein Interactions ◽  
Chemical Biology ◽  
19F Nmr ◽  
Protein Protein Interactions ◽  
Protein Ligand Interactions ◽  
Broad Field ◽  
Ligand Interactions

We previously reviewed the use of 19F NMR in the broad field of chemical biology [Cobb, S. L.; Murphy, C. D. J. Fluorine Chem. 2009, 130, 132–140] and present here a summary of the literature from the last decade that has the technique as the central method of analysis. The topics covered include the synthesis of new fluorinated probes and their incorporation into macromolecules, the application of 19F NMR to monitor protein–protein interactions, protein–ligand interactions, physiologically relevant ions and in the structural analysis of proteins and nucleic acids. The continued relevance of the technique to investigate biosynthesis and biodegradation of fluorinated organic compounds is also described.

Engineering an acetyllysine reader with photocrosslinking amino acid for interactome profiling

2021 ◽  
Author(s):  
Babu Sudhamalla ◽  
Anirban Roy ◽  
Soumen Barman ◽  
Jyotirmayee Padhan
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Protein Interactions ◽  
Unnatural Amino Acids ◽  
Protein Protein Interactions ◽  
Site Specific ◽  
Powerful Approach

The site-specific installation of light-activable crosslinker unnatural amino acids offers a powerful approach to trap transient protein-protein interactions both in vitro and in vivo. Herein, we engineer a bromodomain to...

scholarly journals A phylogenomic analysis of the role and timing of molecular adaptation in the aquatic transition of cetartiodactyl mammals

2015 ◽  
Vol 2 (9) ◽  
pp. 150156 ◽  
Author(s):  
Georgia Tsagkogeorga ◽  
Michael R. McGowen ◽  
Kalina T. J. Davies ◽  
Simon Jarman ◽  
Andrea Polanowski ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Dna Sequences ◽  
Brain Function ◽  
Molecular Adaptation ◽  
Phylogenomic Analysis ◽  
Protein Protein Interactions ◽  
Orthologous Genes ◽  
Genome Wide ◽  
A Genome ◽  
The Common

Recent studies have reported multiple cases of molecular adaptation in cetaceans related to their aquatic abilities. However, none of these has included the hippopotamus, precluding an understanding of whether molecular adaptations in cetaceans occurred before or after they split from their semi-aquatic sister taxa. Here, we obtained new transcriptomes from the hippopotamus and humpback whale, and analysed these together with available data from eight other cetaceans. We identified more than 11 000 orthologous genes and compiled a genome-wide dataset of 6845 coding DNA sequences among 23 mammals, to our knowledge the largest phylogenomic dataset to date for cetaceans. We found positive selection in nine genes on the branch leading to the common ancestor of hippopotamus and whales, and 461 genes in cetaceans compared to 64 in hippopotamus. Functional annotation revealed adaptations in diverse processes, including lipid metabolism, hypoxia, muscle and brain function. By combining these findings with data on protein–protein interactions, we found evidence suggesting clustering among gene products relating to nervous and muscular systems in cetaceans. We found little support for shared ancestral adaptations in the two taxa; most molecular adaptations in extant cetaceans occurred after their split with hippopotamids.

scholarly journals Positive and Negative Regulation of Poly(A) Nuclease

2004 ◽  
Vol 24 (12) ◽  
pp. 5521-5533 ◽  
Author(s):  
David A. Mangus ◽  
Matthew C. Evans ◽  
Nathan S. Agrin ◽  
Mandy Smith ◽  
Preetam Gongidi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Protein Interactions ◽  
Binding Pocket ◽  
Negative Regulation ◽  
Single Amino Acid ◽  
Carboxy Terminus ◽  
Protein Protein Interactions ◽  
C Terminus

ABSTRACT PAN, a yeast poly(A) nuclease, plays an important nuclear role in the posttranscriptional maturation of mRNA poly(A) tails. The activity of this enzyme is dependent on its Pan2p and Pan3p subunits, as well as the presence of poly(A)-binding protein (Pab1p). We have identified and characterized the associated network of factors controlling the maturation of mRNA poly(A) tails in yeast and defined its relevant protein-protein interactions. Pan3p, a positive regulator of PAN activity, interacts with Pab1p, thus providing substrate specificity for this nuclease. Pab1p also regulates poly(A) tail trimming by interacting with Pbp1p, a factor that appears to negatively regulate PAN. Pan3p and Pbp1p both interact with themselves and with the C terminus of Pab1p. However, the domains required for Pan3p and Pbp1p binding on Pab1p are distinct. Single amino acid changes that disrupt Pan3p interaction with Pab1p have been identified and define a binding pocket in helices 2 and 3 of Pab1p's carboxy terminus. The importance of these amino acids for Pab1p-Pan3p interaction, and poly(A) tail regulation, is underscored by experiments demonstrating that strains harboring substitutions in these residues accumulate mRNAs with long poly(A) tails in vivo.

Sign in / Sign up

Export Citation Format

Share Document