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Microbiological Reviews Mar 1995The function and activity of a protein are often modulated by other proteins with which it interacts. This review is intended as a practical guide to the analysis of... (Review)
Review
The function and activity of a protein are often modulated by other proteins with which it interacts. This review is intended as a practical guide to the analysis of such protein-protein interactions. We discuss biochemical methods such as protein affinity chromatography, affinity blotting, coimmunoprecipitation, and cross-linking; molecular biological methods such as protein probing, the two-hybrid system, and phage display: and genetic methods such as the isolation of extragenic suppressors, synthetic mutants, and unlinked noncomplementing mutants. We next describe how binding affinities can be evaluated by techniques including protein affinity chromatography, sedimentation, gel filtration, fluorescence methods, solid-phase sampling of equilibrium solutions, and surface plasmon resonance. Finally, three examples of well-characterized domains involved in multiple protein-protein interactions are examined. The emphasis of the discussion is on variations in the approaches, concerns in evaluating the results, and advantages and disadvantages of the techniques.
Topics: Carrier Proteins; Gene Library; Protein Binding
PubMed: 7708014
DOI: 10.1128/mr.59.1.94-123.1995 -
Drug Discovery Today Jan 2016Most of the small molecules that have been identified thus far to modulate protein-protein interactions (PPIs) are inhibitors. Another promising way to interfere with... (Review)
Review
Most of the small molecules that have been identified thus far to modulate protein-protein interactions (PPIs) are inhibitors. Another promising way to interfere with PPI-associated biological processes is to promote PPI stabilization. Even though PPI stabilizers are still scarce, stabilization of PPIs by small molecules is gaining momentum and offers new pharmacological options. Therefore, we have performed a literature survey of PPI stabilization using small molecules. From this, we propose a classification of PPI stabilizers based on their binding mode and the architecture of the complex to facilitate the structure-based design of stabilizers.
Topics: Biophysical Phenomena; Humans; Protein Binding; Protein Interaction Maps; Small Molecule Libraries
PubMed: 26434617
DOI: 10.1016/j.drudis.2015.09.011 -
Current Pharmaceutical Design 2015Human serum albumin (HSA) is the major plasma protein with vital functions acting as depot and career for many endogenous (fatty acids, bilirubin, etc.) and exogenous... (Review)
Review
Human serum albumin (HSA) is the major plasma protein with vital functions acting as depot and career for many endogenous (fatty acids, bilirubin, etc.) and exogenous substances (drugs, nutrients, etc.) in the blood. Binding to HSA controls the free, active concentration of the drug and may affect considerably the overall pharmacodynamic and pharmacokinetic profile. Studies on drug - protein binding are important from both theoretical and practical point of view as they allow better understanding of the processes underlying drug disposition and elimination and the effect of several pathological states or co-administered drugs on drug delivery and efficacy. The present review focuses on the current state of drug - HSA binding studies. The major functions and consequences of drug - protein binding are described. The X-ray structure of HSA is discussed focusing on the location and the architecture of the primary drug and fatty acids binding sites. Some of the most commonly used methods for drug - HSA binding assay are presented together with examples for their application. The most extensive studied topics in the area are discussed including quantitative characterization of drug - HSA complexation, identification of the binding sites, stereoselectivity of drug - HSA interactions, and thermodynamic characterization of the binding process. A short section is devoted to in silico prediction of drug - HSA binding as an important step in drug design and development.
Topics: Animals; Crystallography, X-Ray; Humans; Pharmaceutical Preparations; Protein Binding; Protein Structure, Secondary; Serum Albumin
PubMed: 25732557
DOI: 10.2174/1381612821666150302113710 -
Biochemical Society Transactions Aug 2007In April 2007, the Biochemical Society held a meeting to compare and contrast ligand binding and activation of Family A and B GPCRs (G-protein-coupled receptors). Being... (Review)
Review
In April 2007, the Biochemical Society held a meeting to compare and contrast ligand binding and activation of Family A and B GPCRs (G-protein-coupled receptors). Being the largest class, Family A GPCRs usually receive the most attention, although a previous Biochemical Society meeting has focused on Family B GPCRs. The aim of the present meeting was to bring researchers of both families together in order to identify commonalities between the two. The present article introduces the proceedings of the meeting, briefly commenting on the focus of each of the following articles.
Topics: Animals; Humans; Ligands; Multigene Family; Protein Binding; Receptors, G-Protein-Coupled
PubMed: 17635129
DOI: 10.1042/BST0350707 -
ChemMedChem Apr 2016At the interface: Guest editors Patrick Gunning and Andrew Wilson summarize the collection of ChemMedChem articles that are part of this joint special issue with...
At the interface: Guest editors Patrick Gunning and Andrew Wilson summarize the collection of ChemMedChem articles that are part of this joint special issue with ChemBioChem focused on protein-protein interactions as targets for therapeutic intervention.
Topics: Drug Discovery; Molecular Targeted Therapy; Protein Binding; Proteins; Small Molecule Libraries
PubMed: 27061459
DOI: 10.1002/cmdc.201600158 -
Trends in Biochemical Sciences Dec 2009How can a single hub protein bind so many different partners? Numerous studies have sought differences between hubs and non-hubs to explain what makes a protein a hub... (Review)
Review
How can a single hub protein bind so many different partners? Numerous studies have sought differences between hubs and non-hubs to explain what makes a protein a hub and how a shared hub-binding site can be promiscuous, yet at the same time be specific. Here, we suggest that the problem is largely non-existent and resides in the popular representation of protein interaction networks: protein products derived from a single gene, even if different, are clustered in maps into a single node. This leads to the impression that a single protein binds to a very large number of partners. In reality, it does not; rather, protein networks reflect the combination of multiple proteins, each with a distinct conformation.
Topics: Models, Biological; Protein Binding; Proteins
PubMed: 19837592
DOI: 10.1016/j.tibs.2009.07.007 -
Bioanalysis Dec 2020The objective of this study was to evaluate the rapid equilibrium dialysis (RED) device in protein binding assays in diluted protein matrices and to improve the...
The objective of this study was to evaluate the rapid equilibrium dialysis (RED) device in protein binding assays in diluted protein matrices and to improve the accuracy of the unbound fraction () measurement. Protein binding assays of drug compounds in bovine serum albumin solutions and human plasma with different folds of dilution were performed using the RED device with and without preconditioning of the dialysis membrane inserts, and the results were compared with those using other approaches in this study. Preconditioning of the RED membrane inserts improved the data accuracy of drug-protein binding assay in matrices with relatively low protein contents and such impact could be compound dependent.
Topics: Blood Proteins; Humans; Pharmaceutical Preparations; Protein Binding
PubMed: 33179537
DOI: 10.4155/bio-2020-0205 -
Nihon Yakurigaku Zasshi. Folia... Aug 2009
Topics: Animals; Drug Interactions; Humans; Protein Binding; Species Specificity
PubMed: 19672002
DOI: 10.1254/fpj.134.78 -
Oncogene Mar 2013A dual role of transforming growth factor β (TGF-β), to both suppress and promote tumor progression and metastasis, has been well established, but its molecular basis... (Review)
Review
A dual role of transforming growth factor β (TGF-β), to both suppress and promote tumor progression and metastasis, has been well established, but its molecular basis has remained elusive. In this review, we focus on Smad proteins, which are central mediators of the signal transduction of TGF-β family members. We describe current knowledge of cell-type-specific binding patterns of Smad proteins and mechanisms of transcriptional regulation, obtained from recent studies on genome-wide binding sites of Smad molecules. We also discuss potential application of the genome-wide analyses for cancer research, which will allow clarification of the complex mechanisms occurring during cancer progression, and the identification of potential biomarkers for future cancer diagnosis, prognosis and therapy.
Topics: Animals; Chromatin Immunoprecipitation; Gene Expression Profiling; Gene Expression Regulation; Genome; Humans; Models, Biological; Oligonucleotide Array Sequence Analysis; Protein Binding; Smad Proteins
PubMed: 22614010
DOI: 10.1038/onc.2012.191 -
Scandinavian Journal of Clinical and... Aug 1970
Topics: Protein Binding; Radioimmunoassay
PubMed: 5457114
DOI: 10.3109/00365517009049205