scholarly journals Stabilization of Haloalkane Dehalogenase Structure by Interfacial Interaction with Ionic Liquids

Crystals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1052
Author(s):  
Anastasiia Shaposhnikova ◽  
Michal Kuty ◽  
Radka Chaloupkova ◽  
Jiri Damborsky ◽  
Ivana Kuta Smatanova ◽  
...  
Keyword(s):  
Ionic Liquids ◽  
Environmental Pollutants ◽  
Three Dimensional ◽  
Structural Basis ◽  
Methyl Sulfate ◽  
Haloalkane Dehalogenase ◽  
Hydrogen Bond Interactions ◽  
Tertiary Protein Structure ◽  
Warfare Agents ◽  
Dynamics Simulations

Ionic liquids attracted interest as green alternatives to replace conventional organic solvents in protein stability studies. They can play an important role in the stabilization of enzymes such as haloalkane dehalogenases that are used for biodegradation of warfare agents and halogenated environmental pollutants. Three-dimensional crystals of haloalkane dehalogenase variant DhaA80 (T148L+G171Q+A172V+C176F) from Rhodococcus rhodochrous NCIMB 13064 were grown and soaked with the solutions of 2-hydroxyethylammonium acetate and 1-butyl-3-methylimidazolium methyl sulfate. The objective was to study the structural basis of the interactions between the ionic liquids and the protein. The diffraction data were collected for the 1.25 Å resolution for 2-hydroxyethylammonium acetate and 1.75 Å resolution for 1-butyl-3-methylimidazolium methyl sulfate. The structures were used for molecular dynamics simulations to study the interactions of DhaA80 with the ionic liquids. The findings provide coherent evidence that ionic liquids strengthen both the secondary and tertiary protein structure due to extensive hydrogen bond interactions.

scholarly journals Structural Basis of the Function of Yariv Reagent—An Important Tool to Study Arabinogalactan Proteins

2021 ◽  
Vol 8 ◽  
Author(s):  
Tereza Přerovská ◽  
Anna Pavlů ◽  
Dzianis Hancharyk ◽  
Anna Rodionova ◽  
Anna Vavříková ◽  
...  
Keyword(s):  
Plant Cell Wall ◽  
Plant Defence ◽  
Three Dimensional ◽  
Arabinogalactan Proteins ◽  
Arabinogalactan Protein ◽  
Dimensional Structure ◽  
Structural Basis ◽  
Functional Studies ◽  
Yariv Reagent ◽  
Dynamics Simulations

Arabinogalactan proteins are very abundant, heavily glycosylated plant cell wall proteins. They are intensively studied because of their crucial role in plant development as well as their function in plant defence. Research of these biomacromolecules is complicated by the lack of tools for their analysis and characterisation due to their extreme heterogeneity. One of the few available tools for detection, isolation, characterisation, and functional studies of arabinogalactan proteins is Yariv reagents. Yariv reagent is a synthetic aromatic glycoconjugate originally prepared as an antigen for immunization. Later, it was found that this compound can precipitate arabinogalactan proteins, namely, their ß-D-(1→3)-galactan structures. Even though this compound has been intensively used for decades, the structural basis of arabinogalactan protein precipitation by Yariv is not known. Multiple biophysical studies have been published, but none of them attempted to elucidate the three-dimensional structure of the Yariv-galactan complex. Here we use a series of molecular dynamics simulations of systems containing one or multiple molecules of ß-D-galactosyl Yariv reagent with or without oligo ß-D-(1→3)-galactan to predict the structure of the complex. According to our model of Yariv-galactan complexes, Yariv reagent forms stacked oligomers stabilized by π-π and CH/π interactions. These oligomers may contain irregularities. Galactan structures crosslink these Yariv oligomers. The results were compared with studies in literature.

scholarly journals Complete structure of the core signalling unit of the E. coli chemosensory array in an optimised minicell strain

2019 ◽  
Author(s):  
Alister Burt ◽  
C. Keith Cassidy ◽  
Peter Ames ◽  
Maria Bacia-Verloop ◽  
Megghane Baulard ◽  
...  
Keyword(s):  
Electron Tomography ◽  
Three Dimensional ◽  
Structural Basis ◽  
Transmembrane Receptors ◽  
Structural Characterisation ◽  
E Coli ◽  
Chemical Gradients ◽  
Membrane Bound ◽  
Subtomogram Averaging ◽  
Dynamics Simulations

Motile bacteria sense chemical gradients with transmembrane receptors organised in supramolecular signalling arrays.1,2 Understanding stimulus detection and transmission at the molecular level requires precise structural characterisation of the array building block known as a core signalling unit (CSU). Here we introduce a novel E. coli strain that forms small minicells possessing extended and highly ordered chemosensory arrays. We provide a three-dimensional (3D) map of a complete CSU at ~16 Å resolution by cryo-electron tomography (cryo-ET) and subtomogram averaging. This map, combined with previously determined high resolution structures and molecular dynamics simulations, yields an atomistic model of the membrane-bound CSU and enables spatial localisation of its signalling domains. Our work thus offers a solid structural basis for interpretation of existing data and design of new experiments to elucidate signalling mechanisms within the CSU and larger array.

Electron Microscopy and image reconstruction reveal the structural basis for spectrin's elastic properties

1992 ◽  
Vol 50 (1) ◽  
pp. 510-511
Author(s):  
Amy M. McGough ◽  
Robert Josephs
Keyword(s):  
Electron Microscopy ◽  
Elastic Properties ◽  
Conformational Changes ◽  
Quaternary Structure ◽  
Three Dimensional ◽  
Membrane Skeleton ◽  
Projection Algorithm ◽  
Structural Basis ◽  
Iterative Approximation ◽  
Membrane Skeletons

The remarkable deformability of the erythrocyte derives in large part from the elastic properties of spectrin, the major component of the membrane skeleton. It is generally accepted that spectrin's elasticity arises from marked conformational changes which include variations in its overall length (1). In this work the structure of spectrin in partially expanded membrane skeletons was studied by electron microscopy to determine the molecular basis for spectrin's elastic properties. Spectrin molecules were analysed with respect to three features: length, conformation, and quaternary structure. The results of these studies lead to a model of how spectrin mediates the elastic deformation of the erythrocyte.Membrane skeletons were isolated from erythrocyte membrane ghosts, negatively stained, and examined by transmission electron microscopy (2). Particle lengths and end-to-end distances were measured from enlarged prints using the computer program MACMEASURE. Spectrin conformation (straightness) was assessed by calculating the particles’ correlation length by iterative approximation (3). Digitised spectrin images were correlation averaged or Fourier filtered to improve their signal-to-noise ratios. Three-dimensional reconstructions were performed using a suite of programs which were based on the filtered back-projection algorithm and executed on a cluster of Microvax 3200 workstations (4).

Designing TIMP (tissue inhibitor of metalloproteinases) variants that are selective metalloproteinase inhibitors

2003 ◽  
Vol 70 ◽  
pp. 201-212 ◽  
Author(s):  
Hideaki Nagase ◽  
Keith Brew
Keyword(s):  
Three Dimensional ◽  
Therapeutic Interventions ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Structural Basis ◽  
Structural Elements ◽  
Ridge Structure ◽  
Extracellular Matrix Components ◽  
Metalloproteinase Inhibitors ◽  
The Matrix ◽  
A Disintegrin And Metalloproteinase

The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of the matrix metalloproteinases (MMPs), enzymes that play central roles in the degradation of extracellular matrix components. The balance between MMPs and TIMPs is important in the maintenance of tissues, and its disruption affects tissue homoeostasis. Four related TIMPs (TIMP-1 to TIMP-4) can each form a complex with MMPs in a 1:1 stoichiometry with high affinity, but their inhibitory activities towards different MMPs are not particularly selective. The three-dimensional structures of TIMP-MMP complexes reveal that TIMPs have an extended ridge structure that slots into the active site of MMPs. Mutation of three separate residues in the ridge, at positions 2, 4 and 68 in the amino acid sequence of the N-terminal inhibitory domain of TIMP-1 (N-TIMP-1), separately and in combination has produced N-TIMP-1 variants with higher binding affinity and specificity for individual MMPs. TIMP-3 is unique in that it inhibits not only MMPs, but also several ADAM (a disintegrin and metalloproteinase) and ADAMTS (ADAM with thrombospondin motifs) metalloproteinases. Inhibition of the latter groups of metalloproteinases, as exemplified with ADAMTS-4 (aggrecanase 1), requires additional structural elements in TIMP-3 that have not yet been identified. Knowledge of the structural basis of the inhibitory action of TIMPs will facilitate the design of selective TIMP variants for investigating the biological roles of specific MMPs and for developing therapeutic interventions for MMP-associated diseases.

Clustering and Sampling of the c-Met Conformational Space: A Computational Drug Discovery Study

2020 ◽  
Vol 22 (9) ◽  
pp. 635-648 ◽  
Author(s):  
Korosh Mashayekh ◽  
Shahrzad Sharifi ◽  
Tahereh Damghani ◽  
Maryam Elyasi ◽  
Mohammad S. Avestan ◽  
...  
Keyword(s):  
Critical Role ◽  
Scientific Work ◽  
Binding Mode ◽  
Docking Studies ◽  
Conformational Space ◽  
Hydrogen Bond Interactions ◽  
Docking Program ◽  
Dynamics Simulations ◽  
Computational Drug Discovery ◽  
Dynamic Ensembles

Background: c-Met kinase plays a critical role in a myriad of human cancers, and a massive scientific work was devoted to design more potent inhibitors. Objective: In this study, 16 molecular dynamics simulations of different complexes of potent c-Met inhibitors with U-shaped binding mode were carried out regarding the dynamic ensembles to design novel potent inhibitors. Methods: A cluster analysis was performed, and the most representative frame of each complex was subjected to the structure-based pharmacophore screening. The GOLD docking program investigated the interaction energy and pattern of output hits from the virtual screening. The most promising hits with the highest scoring values that showed critical interactions with c-Met were presented for ADME/Tox analysis. Results: The screening yielded 45,324 hits that all of them were subjected to the docking studies and 10 of them with the highest-scoring values having diverse structures were presented for ADME/Tox analyses. Conclusion: The results indicated that all the hits shared critical Pi-Pi stacked and hydrogen bond interactions with Tyr1230 and Met1160 respectively.

Prediction of Ionic Liquids Properties through Molecular Dynamics Simulations

2014 ◽  
Vol 4 (2) ◽  
pp. 151-172 ◽  
Author(s):  
Marta L.S. Batista ◽  
Joao A.P. Coutinho ◽  
Jose R.B. Gomes
Keyword(s):  
Molecular Dynamics ◽  
Ionic Liquids ◽  
Molecular Dynamics Simulations ◽  
Dynamics Simulations

scholarly journals Rely on Each Other: DNA Binding Cooperativity Shapes p53 Functions in Tumor Suppression and Cancer Therapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2422
Author(s):  
Oleg Timofeev ◽  
Thorsten Stiewe
Keyword(s):  
Cancer Therapy ◽  
Dna Binding ◽  
Cell Fate ◽  
Tumor Suppression ◽  
Quaternary Structure ◽  
Three Dimensional ◽  
Structural Basis ◽  
Sequence Specificity ◽  
Cell Fate Decisions ◽  
Cancer Mutations

p53 is a tumor suppressor that is mutated in half of all cancers. The high clinical relevance has made p53 a model transcription factor for delineating general mechanisms of transcriptional regulation. p53 forms tetramers that bind DNA in a highly cooperative manner. The DNA binding cooperativity of p53 has been studied by structural and molecular biologists as well as clinical oncologists. These experiments have revealed the structural basis for cooperative DNA binding and its impact on sequence specificity and target gene spectrum. Cooperativity was found to be critical for the control of p53-mediated cell fate decisions and tumor suppression. Importantly, an estimated number of 34,000 cancer patients per year world-wide have mutations of the amino acids mediating cooperativity, and knock-in mouse models have confirmed such mutations to be tumorigenic. While p53 cancer mutations are classically subdivided into “contact” and “structural” mutations, “cooperativity” mutations form a mechanistically distinct third class that affect the quaternary structure but leave DNA contacting residues and the three-dimensional folding of the DNA-binding domain intact. In this review we discuss the concept of DNA binding cooperativity and highlight the unique nature of cooperativity mutations and their clinical implications for cancer therapy.

scholarly journals Online biophysical predictions for SARS-CoV-2 proteins

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Luciano Kagami ◽  
Joel Roca-Martínez ◽  
Jose Gavaldá-García ◽  
Pathmanaban Ramasamy ◽  
K. Anton Feenstra ◽  
...  
Keyword(s):  
Protein Sequence ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Static Structure ◽  
Homologous Proteins ◽  
Structure Based Drug Design ◽  
Protein Protein Interaction ◽  
Link Type ◽  
Dynamics Simulations ◽  
Β Sheet

Abstract Background The SARS-CoV-2 virus, the causative agent of COVID-19, consists of an assembly of proteins that determine its infectious and immunological behavior, as well as its response to therapeutics. Major structural biology efforts on these proteins have already provided essential insights into the mode of action of the virus, as well as avenues for structure-based drug design. However, not all of the SARS-CoV-2 proteins, or regions thereof, have a well-defined three-dimensional structure, and as such might exhibit ambiguous, dynamic behaviour that is not evident from static structure representations, nor from molecular dynamics simulations using these structures. Main We present a website (https://bio2byte.be/sars2/) that provides protein sequence-based predictions of the backbone and side-chain dynamics and conformational propensities of these proteins, as well as derived early folding, disorder, β-sheet aggregation, protein-protein interaction and epitope propensities. These predictions attempt to capture the inherent biophysical propensities encoded in the sequence, rather than context-dependent behaviour such as the final folded state. In addition, we provide the biophysical variation that is observed in homologous proteins, which gives an indication of the limits of their functionally relevant biophysical behaviour. Conclusion The https://bio2byte.be/sars2/ website provides a range of protein sequence-based predictions for 27 SARS-CoV-2 proteins, enabling researchers to form hypotheses about their possible functional modes of action.

Three dimensional graphene materials doped with heteroatoms for extraction and adsorption of environmental pollutants in wastewater

2021 ◽  
Vol 39 (1) ◽  
pp. 17-43
Author(s):  
Zhiyong Guo ◽  
Yufeng Feng ◽  
Chen Zhang ◽  
Guihua Huang ◽  
Jinxin Chi ◽  
...  
Keyword(s):  
Environmental Pollutants ◽  
Three Dimensional

scholarly journals Molecular-Level Investigation of Cycloaliphatic Epoxidised Ionic Liquids as a New Generation of Monomers for Versatile Poly(Ionic Liquids)

Polymers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1512
Author(s):  
Baris Demir ◽  
Gabriel Perli ◽  
Kit-ying Chan ◽  
Jannick Duchet-Rumeau ◽  
Sébastien Livi
Keyword(s):  
Ionic Liquids ◽  
Molecular Level ◽  
Computational Approach ◽  
Polymer Materials ◽  
Chemical Structures ◽  
Cycloaliphatic Epoxy ◽  
Polymer Models ◽  
Mechanical Performances ◽  
Dynamics Simulations ◽  
New Generation

Recently, a new generation of polymerised ionic liquids with high thermal stability and good mechanical performances has been designed through novel and versatile cycloaliphatic epoxy-functionalised ionic liquids (CEILs). From these first promising results and unexplored chemical structures in terms of final properties of the PILs, a computational approach based on molecular dynamics simulations has been developed to generate polymer models and predict the thermo–mechanical properties (e.g., glass transition temperature and Young’s modulus) of experimentally investigated CEILs for producing multi-functional polymer materials. Here, a completely reproducible and reliable computational protocol is provided to design, test and tune poly(ionic liquids) based on epoxidised ionic liquid monomers for future multi-functional thermoset polymers.

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