scholarly journals Uranyl Binding to Proteins and Structural-Functional Impacts

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 457 ◽  
Author(s):  
Ying-Wu Lin
Keyword(s):  
Conformational Changes ◽  
Protein Interactions ◽  
Metal Binding ◽  
Structural Information ◽  
Metal Binding Sites ◽  
Biological Remediation ◽  
Protein Dna Interactions ◽  
Ligand Interactions ◽  
Function Relationship ◽  
Relationship Of

The widespread use of uranium for civilian purposes causes a worldwide concern of its threat to human health due to the long-lived radioactivity of uranium and the high toxicity of uranyl ion (UO22+). Although uranyl–protein/DNA interactions have been known for decades, fewer advances are made in understanding their structural-functional impacts. Instead of focusing only on the structural information, this article aims to review the recent advances in understanding the binding of uranyl to proteins in either potential, native, or artificial metal-binding sites, and the structural-functional impacts of uranyl–protein interactions, such as inducing conformational changes and disrupting protein-protein/DNA/ligand interactions. Photo-induced protein/DNA cleavages, as well as other impacts, are also highlighted. These advances shed light on the structure-function relationship of proteins, especially for metalloproteins, as impacted by uranyl–protein interactions. It is desired to seek approaches for biological remediation of uranyl ions, and ultimately make a full use of the double-edged sword of uranium.

scholarly journals Mass Spectrometry-Based Structural Proteomics for Metal Ion/Protein Binding Studies

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 135
Author(s):  
Yanchun Lin ◽  
Michael L. Gross
Keyword(s):  
Mass Spectrometry ◽  
Conformational Changes ◽  
Protein Interactions ◽  
Metal Binding ◽  
Metal Ion ◽  
Photochemical Oxidation ◽  
Structural Proteomics ◽  
Binding Studies ◽  
Ligand Interactions ◽  
Amino Acid Labeling

Metal ions are critical for the biological and physiological functions of many proteins. Mass spectrometry (MS)-based structural proteomics is an ever-growing field that has been adopted to study protein and metal ion interactions. Native MS offers information on metal binding and its stoichiometry. Footprinting approaches coupled with MS, including hydrogen/deuterium exchange (HDX), “fast photochemical oxidation of proteins” (FPOP) and targeted amino-acid labeling, identify binding sites and regions undergoing conformational changes. MS-based titration methods, including “protein–ligand interactions by mass spectrometry, titration and HD exchange” (PLIMSTEX) and “ligand titration, fast photochemical oxidation of proteins and mass spectrometry” (LITPOMS), afford binding stoichiometry, binding affinity, and binding order. These MS-based structural proteomics approaches, their applications to answer questions regarding metal ion protein interactions, their limitations, and recent and potential improvements are discussed here. This review serves as a demonstration of the capabilities of these tools and as an introduction to wider applications to solve other questions.

scholarly journals Protein-assisted RNA fragment docking (RnaX) for modeling RNA–protein interactions using ModelX

2019 ◽  
Vol 116 (49) ◽  
pp. 24568-24573 ◽  
Author(s):  
Javier Delgado Blanco ◽  
Leandro G. Radusky ◽  
Damiano Cianferoni ◽  
Luis Serrano
Keyword(s):  
Conformational Changes ◽  
Protein Design ◽  
Protein Interactions ◽  
Rna Binding ◽  
Structural Information ◽  
Conformational Dynamics ◽  
Computational Cost ◽  
Regulation Of Transcription ◽  
Sequence Specificity ◽  
Protein Interfaces

RNA–protein interactions are crucial for such key biological processes as regulation of transcription, splicing, translation, and gene silencing, among many others. Knowing where an RNA molecule interacts with a target protein and/or engineering an RNA molecule to specifically bind to a protein could allow for rational interference with these cellular processes and the design of novel therapies. Here we present a robust RNA–protein fragment pair-based method, termed RnaX, to predict RNA-binding sites. This methodology, which is integrated into the ModelX tool suite (http://modelx.crg.es), takes advantage of the structural information present in all released RNA–protein complexes. This information is used to create an exhaustive database for docking and a statistical forcefield for fast discrimination of true backbone-compatible interactions. RnaX, together with the protein design forcefield FoldX, enables us to predict RNA–protein interfaces and, when sufficient crystallographic information is available, to reengineer the interface at the sequence-specificity level by mimicking those conformational changes that occur on protein and RNA mutagenesis. These results, obtained at just a fraction of the computational cost of methods that simulate conformational dynamics, open up perspectives for the engineering of RNA–protein interfaces.

ASSOCIATION OF FEATURE GENE EXPRESSION WITH STRUCTURAL FINGERPRINTS OF CHEMICAL COMPOUNDS

2011 ◽  
Vol 09 (04) ◽  
pp. 503-519 ◽  
Author(s):  
YUN LI ◽  
KANG TU ◽  
SIYUAN ZHENG ◽  
JINGFANG WANG ◽  
YIXUE LI ◽  
...  
Keyword(s):  
Gene Expression ◽  
Structural Information ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Structural Difference ◽  
Structural Features ◽  
Molecular Structures ◽  
Transcriptomics Data ◽  
Function Relationship ◽  
Relationship Of

Exploring the relationship between a chemical structure and its biological function is of great importance for drug discovery. For understanding the mechanisms of drug action, researchers traditionally focused on the molecular structures in the context of interactions with targets. The newly emerged high-throughput "omics" technology opened a new dimension to study the structure–function relationship of chemicals. Previous studies made attempts to introduce transcriptomics data into chemical function investigation. But little effort has been made to link structural fingerprints of compounds with defined intracellular functions, i.e. expression of particular genes and altered pathways. By integrating the chemical structural information with the gene expression profiles of chemical-treated cells, we developed a novel method to associate the structural difference between compounds with the expression of a definite set of genes, which were called feature genes. A subtraction protocol was designed to extract a minimum gene set related to chemical structural features, which can be utilized in practice as markers for drug screening. Case studies demonstrated that our approach is capable of finding feature genes associated with chemical structural fingerprints.

scholarly journals Applications of In-Cell NMR in Structural Biology and Drug Discovery

2019 ◽  
Vol 20 (1) ◽  
pp. 139 ◽  
Author(s):  
CongBao Kang
Keyword(s):  
Drug Discovery ◽  
Conformational Changes ◽  
Protein Interactions ◽  
Mammalian Cells ◽  
Structural Information ◽  
Living Cells ◽  
Bacterial Cells ◽  
Protein Protein Interactions ◽  
Nmr Studies ◽  
Post Translational Modifications

In-cell nuclear magnetic resonance (NMR) is a method to provide the structural information of a target at an atomic level under physiological conditions and a full view of the conformational changes of a protein caused by ligand binding, post-translational modifications or protein–protein interactions in living cells. Previous in-cell NMR studies have focused on proteins that were overexpressed in bacterial cells and isotopically labeled proteins injected into oocytes of Xenopus laevis or delivered into human cells. Applications of in-cell NMR in probing protein modifications, conformational changes and ligand bindings have been carried out in mammalian cells by monitoring isotopically labeled proteins overexpressed in living cells. The available protocols and successful examples encourage wide applications of this technique in different fields such as drug discovery. Despite the challenges in this method, progress has been made in recent years. In this review, applications of in-cell NMR are summarized. The successful applications of this method in mammalian and bacterial cells make it feasible to play important roles in drug discovery, especially in the step of target engagement.

scholarly journals Proteopedia: Bridging the Rift Between 3D Structure & Function of Biomacromolecules

2014 ◽  
Vol 70 (a1) ◽  
pp. C1388-C1388
Author(s):  
Joel Sussman ◽  
Jaime Prilusky
Keyword(s):  
Structure Function ◽  
Scientific Community ◽  
Structural Information ◽  
3D Structure ◽  
Hiv Protease ◽  
3D Images ◽  
Web Resource ◽  
Complex Structural ◽  
Function Relationship ◽  
Relationship Of

Proteopedia is a wiki web resource, http://proteopedia.org, which aids in understanding of the structure/function relationship of biomacromolecules. The `3D' images on each page are surrounded by descriptive text containing hyperlinks that change the appearance (view, representations, colors or labels) of the adjacent 3D structure to reflect the concept discussed in the text (see figure below). This makes the complex structural information readily accessible and comprehensible, even to non-structural biologists. Using Proteopedia, scientists and students can easily create descriptions of biomacromolecules linked to their 3D structure, e.g., a page on the way inhibitors block HIV Protease, http://proteopedia.org/w/HIV-1_protease. Pages can be viewed on computers and tablets via the molecular viewer JSmol. Content is being added by ~2,600 Proteopedia's users from more than 50 countries, in a dozen different languages, including Arabic, Russian & Chinese. Members of the scientific community are invited to request a Proteopedia user account, at no cost, to create and edit pages, see: http://proteopedia.org/w/Special:RequestAccount.

Nitrogen- and sulfur-containing models for metallo-enzymes. Part I. Synthesis and physical studies of 2(2-pyridyl)-1,3-dithioalkyl-2-propanols, 2(2-pyridyl)- and 2(2-imidazolyl)-1,3-dimercapto-2-propanols

1981 ◽  
Vol 59 (1) ◽  
pp. 65-75 ◽  
Author(s):  
N. J. Curtis ◽  
R. S. Brown
Keyword(s):  
Small Molecule ◽  
Metal Binding ◽  
Binding Sites ◽  
Divalent Metals ◽  
Metal Binding Sites ◽  
Ph Values ◽  
Biochemical Systems ◽  
Relationship Of ◽  
The Relationship ◽  
Sulfur Containing

Several compounds of the title class have been synthesized as small-molecule analogues for the metal-binding sites in such biochemical systems as ADH. The ligands containing pyridine and two thioethers do not bind divalent metals (Co2+, Zn2+, Cu2+, Ni2+), strongly suggesting that thioethers are poorly chelated. However, the analogues containing free SH groups bind divalent metals very strongly, producing complexes with limited solubility at pH values in excess of 6. Titration of the latter ligands in the presence of 1 equiv. Zn2+ indicates the consumption of 3 equiv. OH− by pH 6, one for the [Formula: see text] ionization, and one for each S—H bound to Zn2+. On the basis of these data the resulting complexes are considered to neutral bis-thiolates. The relationship of these data to the state of ionization of the Zn2+-cysteine SH's in ADH is discussed.

Time-resolved footprinting for the study of the structural dynamics of DNA–protein interactions

2008 ◽  
Vol 36 (4) ◽  
pp. 745-748 ◽  
Author(s):  
Bianca Sclavi
Keyword(s):  
Rna Polymerase ◽  
Conformational Changes ◽  
Protein Interactions ◽  
Structural Information ◽  
Double Helix ◽  
High Temporal Resolution ◽  
Kinetic Properties ◽  
Time Resolved ◽  
Sequence Recognition

Transcription is often regulated at the level of initiation by the presence of transcription factors or nucleoid proteins or by changing concentrations of metabolites. These can influence the kinetic properties and/or structures of the intermediate RNA polymerase–DNA complexes in the pathway. Time-resolved footprinting techniques combine the high temporal resolution of a stopped-flow apparatus with the specific structural information obtained by the probing agent. Combined with a careful quantitative analysis of the evolution of the signals, this approach allows for the identification and kinetic and structural characterization of the intermediates in the pathway of DNA sequence recognition by a protein, such as a transcription factor or RNA polymerase. The combination of different probing agents is especially powerful in revealing different aspects of the conformational changes taking place at the protein–DNA interface. For example, hydroxyl radical footprinting, owing to their small size, provides a map of the solvent-accessible surface of the DNA backbone at a single nucleotide resolution; modification of the bases using potassium permanganate can reveal the accessibility of the bases when the double helix is distorted or melted; cross-linking experiments report on the formation of specific amino acid–DNA contacts, and DNase I footprinting results in a strong signal-to-noise ratio from DNA protection at the binding site and hypersensitivity at curved or kinked DNA sites. Recent developments in protein footprinting allow for the direct characterization of conformational changes of the proteins in the complex.

Conformational changes in the metal-binding sites of cardiac troponin C induced by calcium binding

Biochemistry ◽  
1992 ◽  
Vol 31 (6) ◽  
pp. 1595-1602 ◽  
Author(s):  
George A. Krudy ◽  
Rui M. M. Brito ◽  
John A. Putkey ◽  
Paul R. Rosevear
Keyword(s):  
Conformational Changes ◽  
Metal Binding ◽  
Binding Sites ◽  
Calcium Binding ◽  
Cardiac Troponin ◽  
Troponin C ◽  
Metal Binding Sites ◽  
Cardiac Troponin C

scholarly journals Superresolution imaging reveals structural features of EB1 in microtubule plus-end tracking

2014 ◽  
Vol 25 (25) ◽  
pp. 4166-4173 ◽  
Author(s):  
Peng Xia ◽  
Xing Liu ◽  
Bing Wu ◽  
Shuyuan Zhang ◽  
Xiaoyu Song ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Fluorescent Protein ◽  
Critical Role ◽  
Conformational Dynamics ◽  
Spatial Dynamics ◽  
Structural Features ◽  
Live Cells ◽  
Culture Cells ◽  
Function Relationship ◽  
Relationship Of

Visualization of specific molecules and their interactions in real time and space is essential to delineate how cellular dynamics and the signaling circuit are orchestrated. Spatial regulation of conformational dynamics and structural plasticity of protein interactions is required to rewire signaling circuitry in response to extracellular cues. We introduce a method for optically imaging intracellular protein interactions at nanometer spatial resolution in live cells, using photoactivatable complementary fluorescent (PACF) proteins. Subsets of complementary fluorescent protein molecules were activated, localized, and then bleached; this was followed by the assembly of superresolution images from aggregate position of sum interactive molecules. Using PACF, we obtained precise localization of dynamic microtubule plus-end hub protein EB1 dimers and their distinct distributions at the leading edges and in the cell bodies of migrating cells. We further delineated the structure–function relationship of EB1 by generating EB1-PACF dimers (EB1wt:EB1wt, EB1wt:EB1mt, and EB1mt:EB1mt) and imaging their precise localizations in culture cells. Surprisingly, our analyses revealed critical role of a previously uncharacterized EB1 linker region in tracking microtubule plus ends in live cells. Thus PACF provides a unique approach to delineating spatial dynamics of homo- or heterodimerized proteins at the nanometer scale and establishes a platform to report the precise regulation of protein interactions in space and time in live cells.

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