Insights into the molecular features of the von Hippel-Lindau like protein

2018 ◽  
Author(s):  
Federica Quaglia ◽  
Giovanni Minervini ◽  
Francesco Tabaro ◽  
Silvio C.E. Tosatto
Keyword(s):  
Three Dimensional ◽  
Binding Activity ◽  
Dynamics Simulation ◽  
Tumor Suppressor Protein ◽  
Multiple Functions ◽  
Functional Roles ◽  
Von Hippel Lindau ◽  
Molecular Features ◽  
Protein Interfaces

AbstractWe present an in silico characterization of the von Hippel-Lindau like protein (VLP), the only known human paralogue of the von Hippel-Lindau tumor suppressor protein (pVHL). Phylogenetic investigation showed VLP to be mostly conserved in upper mammals and specifically expressed in brain and testis. Structural analysis and molecular dynamics simulation show VLP to be very similar to pVHL three-dimensional organization and binding dynamics. In particular, conservation of elements at the protein interfaces suggests VLP to be a functional pVHL homolog potentially possessing multiple functions beyond HIF-1α-dependent binding activity. Our findings show that VLP may share at least seven interactors with pVHL, suggesting novel functional roles for this under-studied human protein. These may occur at precise hypoxia levels where functional overlap with pVHL may permit a finer modulation of pVHL functions.

Characterization of photosystem II with the atomic-force microscope

1992 ◽  
Vol 50 (2) ◽  
pp. 1146-1147
Author(s):  
Kathleen M. Marr ◽  
Mary K. Lyon
Keyword(s):  
Photosystem Ii ◽  
Atomic Force Microscope ◽  
Three Dimensional ◽  
Biologically Active ◽  
Atomic Force ◽  
Freeze Etching ◽  
Image Averaging ◽  
Oxygen Evolving ◽  
Averaging Techniques

Photosystem II (PSII) is different from all other reaction centers in that it splits water to evolve oxygen and hydrogen ions. This unique ability to evolve oxygen is partly due to three oxygen evolving polypeptides (OEPs) associated with the PSII complex. Freeze etching on grana derived insideout membranes revealed that the OEPs contribute to the observed tetrameric nature of the PSIl particle; when the OEPs are removed, a distinct dimer emerges. Thus, the surface of the PSII complex changes dramatically upon removal of these polypeptides. The atomic force microscope (AFM) is ideal for examining surface topography. The instrument provides a topographical view of individual PSII complexes, giving relatively high resolution three-dimensional information without image averaging techniques. In addition, the use of a fluid cell allows a biologically active sample to be maintained under fully hydrated and physiologically buffered conditions. The OEPs associated with PSII may be sequentially removed, thereby changing the surface of the complex by one polypeptide at a time.

convergent-beam diffraction from surfaces

1987 ◽  
Vol 45 ◽  
pp. 30-33
Author(s):  
J. A. Eades ◽  
A. E. Smith ◽  
D. F. Lynch
Keyword(s):  
Reciprocal Lattice ◽  
Three Dimensional ◽  
Grazing Incidence ◽  
Three Dimensions ◽  
Plane Figure ◽  
Transmission Electron ◽  
Convergent Beam ◽  
Beam Patterns ◽  
Beam Diffraction

It is quite simple (in the transmission electron microscope) to obtain convergent-beam patterns from the surface of a bulk crystal. The beam is focussed onto the surface at near grazing incidence (figure 1) and if the surface is flat the appropriate pattern is obtained in the diffraction plane (figure 2). Such patterns are potentially valuable for the characterization of surfaces just as normal convergent-beam patterns are valuable for the characterization of crystals.There are, however, several important ways in which reflection diffraction from surfaces differs from the more familiar electron diffraction in transmission.GeometryIn reflection diffraction, because of the surface, it is not possible to describe the specimen as periodic in three dimensions, nor is it possible to associate diffraction with a conventional three-dimensional reciprocal lattice.

Construction of plastic contact deformation maps on ceramics: a case study on aluminum nitride

1996 ◽  
Vol 54 ◽  
pp. 636-637
Author(s):  
D. L. Callahan
Keyword(s):  
Plastic Deformation ◽  
Aluminum Nitride ◽  
Mechanical Response ◽  
Three Dimensional ◽  
Bright Field Image ◽  
Perfectly Plastic ◽  
Contrast Analysis ◽  
Deformation Patterns

Modern polishing, precision machining and microindentation techniques allow the processing and mechanical characterization of ceramics at nanometric scales and within entirely plastic deformation regimes. The mechanical response of most ceramics to such highly constrained contact is not predictable from macroscopic properties and the microstructural deformation patterns have proven difficult to characterize by the application of any individual technique. In this study, TEM techniques of contrast analysis and CBED are combined with stereographic analysis to construct a three-dimensional microstructure deformation map of the surface of a perfectly plastic microindentation on macroscopically brittle aluminum nitride.The bright field image in Figure 1 shows a lg Vickers microindentation contained within a single AlN grain far from any boundaries. High densities of dislocations are evident, particularly near facet edges but are not individually resolvable. The prominent bend contours also indicate the severity of plastic deformation. Figure 2 is a selected area diffraction pattern covering the entire indentation area.

Characterization of a monolayer graphitic structure

1994 ◽  
Vol 52 ◽  
pp. 760-761
Author(s):  
X. Lin ◽  
X. K. Wang ◽  
V. P. Dravid ◽  
J. B. Ketterson ◽  
R. P. H. Chang
Keyword(s):  
Three Dimensional ◽  
Single Layer ◽  
Synthesis Process ◽  
Graphitic Structure ◽  
Positive Gaussian Curvature ◽  
Graphitic Sheet ◽  
Structural And Electronic Properties ◽  
New Material ◽  
Hexagonal Network

For small curvatures of a graphitic sheet, carbon atoms can maintain their preferred sp2 bonding while allowing the sheet to have various three-dimensional geometries, which may have exotic structural and electronic properties. In addition the fivefold rings will lead to a positive Gaussian curvature in the hexagonal network, and the sevenfold rings cause a negative one. By combining these sevenfold and fivefold rings with sixfold rings, it is possible to construct complicated carbon sp2 networks. Because it is much easier to introduce pentagons and heptagons into the single-layer hexagonal network than into the multilayer network, the complicated morphologies would be more common in the single-layer graphite structures. In this contribution, we report the observation and characterization of a new material of monolayer graphitic structure by electron diffraction, HREM, EELS.The synthesis process used in this study is reported early. We utilized a composite anode of graphite and copper for arc evaporation in helium.

Characterization of Monoclonal Anti-human Factor VII Antibody (B101/B1) that Recognized Three-dimensional Structures near Arg at Position 79 in the First EGF-like Domain

1998 ◽  
Vol 79 (01) ◽  
pp. 104-109 ◽  
Author(s):  
Osamu Takamiya
Keyword(s):  
Monoclonal Antibodies ◽  
Tissue Factor ◽  
Human Factor ◽  
Solid Phase ◽  
Three Dimensional ◽  
Coagulation Factors ◽  
Factor Vii ◽  
Dimensional Structure ◽  
Epidermal Growth

SummaryMurine monoclonal antibodies (designated hVII-B101/B1, hVIIDC2/D4 and hVII-DC6/3D8) directed against human factor VII (FVII) were prepared and characterized, with more extensive characterization of hVII-B101/B1 that did not bind reduced FVIIa. The immunoglobulin of the three monoclonal antibodies consisted of IgG1. These antibodies did not inhibit procoagulant activities of other vitamin K-dependent coagulation factors except FVII and did not cross-react with proteins in the immunoblotting test. hVII-DC2/D4 recognized the light chain after reduction of FVIIa with 2-mercaptoethanol, and hVIIDC6/3D8 the heavy chain. hVII-B101/B1 bound FVII without Ca2+, and possessed stronger affinity for FVII in the presence of Ca2+. The Kd for hVII-B101/B1 to FVII was 1.75 x 10–10 M in the presence of 5 mM CaCl2. The antibody inhibited the binding of FVII to tissue factor in the presence of Ca2+. hVII-B101/B1 also inhibited the activation of FX by the complex of FVIIa and tissue factor in the presence of Ca2+. Furthermore, immunoblotting revealed that hVII-B101/B1 reacted with non-reduced γ-carboxyglutaminic acid (Gla)-domainless-FVII and/or FVIIa. hVII-B101/B1 showed a similar pattern to that of non-reduced proteolytic fragments of FVII by trypsin with hVII-DC2/D4 on immunoblotting test. hVII-B101/B1 reacted differently with the FVII from the dysfunctional FVII variant, FVII Shinjo, which has a substitution of Gln for Arg at residue 79 in the first epidermal growth factor (1st EGF)-like domain (Takamiya O, et al. Haemosta 25, 89-97,1995) compared with normal FVII, when used as a solid phase-antibody for ELISA by the sandwich method. hVII-B101/B1 did not react with a series of short peptide sequences near position 79 in the first EGF-like domain on the solid-phase support for epitope scanning. These results suggested that the specific epitope of the antibody, hVII-B101/B1, was located in the three-dimensional structure near position 79 in the first EGF-like domain of human FVII.

Thermal characterization of ABS-Graphene blended three dimensional printed functional prototypes for electro chemical energy storage

2018 ◽  
Vol 1 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Kamaljit Singh Boparai ◽  
Rupinder Singh
Keyword(s):  
Energy Storage ◽  
Structural Changes ◽  
Fused Deposition Modeling ◽  
Morphological Changes ◽  
Three Dimensional ◽  
Thermal Characterization ◽  
Chemical Energy ◽  
Flow Index ◽  
Fused Deposition

This study highlights the thermal characterization of ABS-Graphene blended three dimensional (3D) printed functional prototypes by fused deposition modeling (FDM) process. These functional prototypes have some applications as electro-chemical energy storage devices (EESD). Initially, the suitability of ABS-Graphene composite material for FDM applications has been examined by melt flow index (MFI) test. After establishing MFI, the feedstock filament for FDM has been prepared by an extrusion process. The fabricated filament has been used for printing 3D functional prototypes for printing of in-house EESD. The differential scanning calorimeter (DSC) analysis was conducted to understand the effect on glass transition temperature with the inclusion of Graphene (Gr) particles. It has been observed that the reinforced Gr particles act as a thermal reservoir (sink) and enhances its thermal/electrical conductivity. Also, FT-IR spectra realized the structural changes with the inclusion of Gr in ABS matrix. The results are supported by scanning electron microscopy (SEM) based micrographs for understanding the morphological changes.

Interpretable SMILES-based QSAR model of inhibitory activity of sirtuins 1 and 2

2020 ◽  
Vol 23 ◽  
Author(s):  
Apilak Worachartcheewan ◽  
Alla P. Toropova ◽  
Andrey A. Toropov ◽  
Reny Pratiwi ◽  
Virapong Prachayasittikul ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Rational Design ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Sirtuin 1 ◽  
Data Set ◽  
Functional Roles ◽  
Molecular Features ◽  
Oecd Principles ◽  
Qsar Models

Background: Sirtuin 1 (Sirt1) and sirtuin 2 (Sirt2) are NAD+ -dependent histone deacetylases which play important functional roles in removal of the acetyl group of acetyl-lysine substrates. Considering the dysregulation of Sirt1 and Sirt2 as etiological causes of diseases, Sirt1 and Sirt2 are lucrative target proteins for treatment, thus there has been great interest in the development of Sirt1 and Sirt2 inhibitors. Objective: This study compiled the bioactivity data of Sirt1 and Sirt2 for the construction of quantitative structure-activity relationship (QSAR) models in accordance with the OECD principles. Method: Simplified molecular input line entry system (SMILES)-based molecular descriptors were used to characterize the molecular features of inhibitors while the Monte Carlo method of the CORAL software was employed for multivariate analysis. The data set was subjected to 3 random splits in which each split separated the data into 4 subsets consisting of training, invisible training, calibration and external sets. Results: Statistical indices for the evaluation of QSAR models suggested good statistical quality for models of Sirt1 and Sirt2 inhibitors. Furthermore, mechanistic interpretation of molecular substructures that are responsible for modulating the bioactivity (i.e. promoters of increase or decrease of bioactivity) was extracted via the analysis of correlation weights. It exhibited molecular features involved Sirt1 and Sirt2 inhibitors. Conclusion: It is anticipated that QSAR models presented herein can be useful as guidelines in the rational design of potential Sirt1 and Sirt2 inhibitors for the treatment of Sirtuin-related diseases.

In Silico Identification and Molecular Characterization of Extracellular Cathepsin L Proteases from Giardia duodenalis

2020 ◽  
Vol 17 (4) ◽  
pp. 342-351
Author(s):  
Sergio A. Durán-Pérez ◽  
José G. Rendón-Maldonado ◽  
Lucio de Jesús Hernandez-Diaz ◽  
Annete I. Apodaca-Medina ◽  
Maribel Jiménez-Edeza ◽  
...  
Keyword(s):  
In Silico ◽  
Cathepsin L ◽  
Three Dimensional ◽  
Giardia Duodenalis ◽  
Evolutionary Genetics ◽  
Extracellular Proteins ◽  
In Silico Identification ◽  
Dimensional Models ◽  
Three Dimensional Models

Background: The protozoan Giardia duodenalis, which causes giardiasis, is an intestinal parasite that commonly affects humans, mainly pre-school children. Although there are asymptomatic cases, the main clinical features are chronic and acute diarrhea, nausea, abdominal pain, and malabsorption syndrome. Little is currently known about the virulence of the parasite, but some cases of chronic gastrointestinal alterations post-infection have been reported even when the infection was asymptomatic, suggesting that the cathepsin L proteases of the parasite may be involved in the damage at the level of the gastrointestinal mucosa. Objective: The aim of this study was the in silico identification and characterization of extracellular cathepsin L proteases in the proteome of G. duodenalis. Methods: The NP_001903 sequence of cathepsin L protease from Homo sapienswas searched against the Giardia duodenalisproteome. The subcellular localization of Giardia duodenaliscathepsin L proteases was performed in the DeepLoc-1.0 server. The construction of a phylogenetic tree of the extracellular proteins was carried out using the Molecular Evolutionary Genetics Analysis software (MEGA X). The Robetta server was used for the construction of the three-dimensional models. The search for possible inhibitors of the extracellular cathepsin L proteases of Giardia duodenaliswas performed by entering the three-dimensional structures in the FINDSITEcomb drug discovery tool. Results: Based on the amino acid sequence of cathepsin L from Homo sapiens, 8 protein sequences were identified that have in their modular structure the Pept_C1A domain characteristic of cathepsins and two of these proteins (XP_001704423 and XP_001704424) are located extracellularly. Threedimensional models were designed for both extracellular proteins and several inhibitory ligands with a score greater than 0.9 were identified. In vitrostudies are required to corroborate if these two extracellular proteins play a role in the virulence of Giardia duodenalisand to discover ligands that may be useful as therapeutic targets that interfere in the mechanism of pathogenesis generated by the parasite. Conclusion: In silicoanalysis identified two proteins in the Giardia duodenalisprotein repertoire whose characteristics allowed them to be classified as cathepsin L proteases, which may be secreted into the extracellular medium to act as virulence factors. Three-dimensional models of both proteins allowed the identification of inhibitory ligands with a high score. The results suggest that administration of those compounds might be used to block the endopeptidase activity of the extracellular cathepsin L proteases, interfering with the mechanisms of pathogenesis of the protozoan parasite Giardia duodenalis.

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