Glomerular B2-kinin-binding sites in two-kidney, one-clip hypertensive rats

1991 ◽  
Vol 260 (5) ◽  
pp. F626-F634 ◽  
Author(s):  
C. Emond ◽  
J. L. Bascands ◽  
J. Rakotoarivony ◽  
F. Praddaude ◽  
G. Bompart ◽  
...  
Keyword(s):  
Binding Sites ◽  
Protein A ◽  
Three Dimensional ◽  
Compensatory Hypertrophy ◽  
Dimensional Structure ◽  
Hypertensive Rats ◽  
The Difference ◽  
Pg E2 ◽  
Kallikrein Activity ◽  
Area And Volume

To extend our recent observations of the possible downregulation of glomerular B2-kinin-binding sites, we investigated density (Bmax) of bradykinin (BK)-binding sites in glomerular membranes of both the clipped (C) and nonclipped (NC) kidneys of two-kidney, one-clip (2K-1C) Goldblatt hypertensive rats, in relation to tissue kallikrein activity and glomerular three-dimensional structure. Compared with the Bmax of sham-operated (SO) kidney (31.8 +/- 7 fmol/mg protein), a significant increase in Bmax was observed in glomeruli of both kidneys in hypertensive rats, the Bmax being higher in glomeruli of NC than in C kidneys (98 +/- 11 vs. 59 +/- 12 fmol/mg protein). NC kidney compensatory hypertrophy was expressed by an increase in glomerular diameter, surface area, and volume. When expressed per unit of area or volume, Bmax in NC kidneys remained significantly higher than in both C and SO kidneys. Increased Bmax in both kidneys of 2K-1C rats was associated with a decreased intrarenal level of kallikrein. We also examined prostaglandin (PG) E2 release by isolated glomeruli from SO, C, and NC kidneys as a possible biological effect induced by BK. Whereas C kidney released more PGE2 than NC kidney under basal conditions, addition of BK (10 nM) induced greater PGE2 production in NC kidney consistent with the difference in Bmax between C and NC kidneys. These results suggest a possible downregulation of glomerular B2-binding sites by bradykinin, which may explain the difference between SO and C kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Conformation of Ribosomes from Escherichia Coli

1974 ◽  
Vol 32 ◽  
pp. 210-211
Author(s):  
M. Boublik ◽  
W. Hellmann ◽  
F. Jenkins
Keyword(s):  
Binding Sites ◽  
Ribosomal Proteins ◽  
Fluorescent Dyes ◽  
Protein Biosynthesis ◽  
Three Dimensional ◽  
Spatial Arrangement ◽  
Dimensional Structure ◽  
Complete Understanding ◽  
And Function

The present knowledge of the three-dimensional structure of ribosomes is far too limited to enable a complete understanding of the various roles which ribosomes play in protein biosynthesis. The spatial arrangement of proteins and ribonuclec acids in ribosomes can be analysed in many ways. Determination of binding sites for individual proteins on ribonuclec acid and locations of the mutual positions of proteins on the ribosome using labeling with fluorescent dyes, cross-linking reagents, neutron-diffraction or antibodies against ribosomal proteins seem to be most successful approaches. Structure and function of ribosomes can be correlated be depleting the complete ribosomes of some proteins to the functionally inactive core and by subsequent partial reconstitution in order to regain active ribosomal particles.

scholarly journals Determination of the alpha-actinin-binding site on actin filaments by cryoelectron microscopy and image analysis.

1994 ◽  
Vol 126 (2) ◽  
pp. 433-443 ◽  
Author(s):  
A McGough ◽  
M Way ◽  
D DeRosier
Keyword(s):  
Image Analysis ◽  
Smooth Muscle ◽  
Binding Sites ◽  
Actin Filaments ◽  
Three Dimensional ◽  
Actin Binding ◽  
Dimensional Structure ◽  
Outer Face ◽  
Actin Binding Domain

The three-dimensional structure of actin filaments decorated with the actin-binding domain of chick smooth muscle alpha-actinin (alpha A1-2) has been determined to 21-A resolution. The shape and location of alpha A1-2 was determined by subtracting maps of F-actin from the reconstruction of decorated filaments. alpha A1-2 resembles a bell that measures approximately 38 A at its base and extends 42 A from its base to its tip. In decorated filaments, the base of alpha A1-2 is centered about the outer face of subdomain 2 of actin and contacts subdomain 1 of two neighboring monomers along the long-pitch (two-start) helical strands. Using the atomic model of F-actin (Lorenz, M., D. Popp, and K. C. Holmes. 1993. J. Mol. Biol. 234:826-836.), we have been able to test directly the likelihood that specific actin residues, which have been previously identified by others, interact with alpha A1-2. Our results indicate that residues 86-117 and 350-375 comprise distinct binding sites for alpha-actinin on adjacent actin monomers.

scholarly journals Disruption of the utrophin–actin interaction by monoclonal antibodies and prediction of an actin-binding surface of utrophin

1998 ◽  
Vol 337 (1) ◽  
pp. 119-123 ◽  
Author(s):  
Glenn E. MORRIS ◽  
Nguyen thi MAN ◽  
Nguyen thi Ngoc HUYEN ◽  
Alexander PEREBOEV ◽  
John KENDRICK-JONES ◽  
...  
Keyword(s):  
Binding Sites ◽  
Three Dimensional ◽  
Binding Domain ◽  
Actin Binding ◽  
Dimensional Structure ◽  
Functional Regions ◽  
Binding Surface ◽  
Actin Binding Domain ◽  
Actin Binding Site ◽  
Helical Region

Monoclonal antibody (mAb) binding sites in the N-terminal actin-binding domain of utrophin have been identified using phage-displayed peptide libraries, and the mAbs have been used to probe functional regions of utrophin involved in actin binding. mAbs were characterized for their ability to interact with the utrophin actin-binding domain and to affect actin binding to utrophin in sedimentation assays. One of these antibodies was able to inhibit utrophin–F-actin binding and was shown to recognize a predicted helical region at residues 13–22 of utrophin, close to a previously predicted actin-binding site. Two other mAbs which did not affect actin binding recognized predicted loops in the second calponin homology domain of the utrophin actin-binding domain. Using the known three-dimensional structure of the homologous actin-binding domain of fimbrin, these results have enabled us to determine the likely orientation of the utrophin actin-binding domain with respect to the actin filament.

scholarly journals BiRDS - Binding Residue Detection from Protein Sequences using Deep ResNets

2021 ◽  
Author(s):  
Vineeth Chelur ◽  
U. Deva Priyakumar
Keyword(s):  
Binding Site ◽  
Binding Sites ◽  
Tertiary Structure ◽  
Solvent Accessibility ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Relative Solvent Accessibility ◽  
Single Chain ◽  
Sequence Alignments ◽  
Multiple Sequence

Protein-drug interactions play important roles in many biological processes and therapeutics. Prediction of the active binding site of a protein helps discover and optimise these interactions leading to the design of better ligand molecules. The tertiary structure of a protein determines the binding sites available to the drug molecule. A quick and accurate prediction of the binding site from sequence alone without utilising the three-dimensional structure is challenging. Deep Learning has been used in a variety of biochemical tasks and has been hugely successful. In this paper, a Residual Neural Network (leveraging skip connections) is implemented to predict a protein's most active binding site. An Annotated Database of Druggable Binding Sites from the Protein DataBank, sc-PDB, is used for training the network. Features extracted from the Multiple Sequence Alignments (MSAs) of the protein generated using DeepMSA, such as Position-Specific Scoring Matrix (PSSM), Secondary Structure (SS3), and Relative Solvent Accessibility (RSA), are provided as input to the network. A weighted binary cross-entropy loss function is used to counter the substantial imbalance in the two classes of binding and non-binding residues. The network performs very well on single-chain proteins, providing a pocket that has good interactions with a ligand.

scholarly journals Identification of biomolecules for Alzheimer's disease using docking analysis of tau protein

2021 ◽  
pp. 192-203
Author(s):  
Mansi Agrahari ◽  
Kanu Megha ◽  
Kajal Dahiya ◽  
Ila Sharma ◽  
Ankur Sharma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Active Site ◽  
Protein A ◽  
Three Dimensional ◽  
Docking Studies ◽  
Dimensional Structure ◽  
Docking Analysis ◽  
Bioinformatic Tools

Objective: In-silico methods to find and characterize the ligands against the active site of tau protein which could assist in the therapeutics of Alzheimer's disease. Methods: The aid of various bioinformatic tools such as phylogenetic analysis, homology modeling, and active site prediction led to the molecular docking analysis of the major malefactor for Alzheimer’s disease ‘microtubule- associated tau protein’. A three-dimensional structure of microtubule-related tau protein was created, and the Ramachandran plot was acquired for quality appraisal. Results: Procheck showed 62.95 of residues in the most preferred region with 20% residues in the additional allowed region and 5.7 % in the disallowed region of microtubule-associated tau protein. Screenings of the particles were done dependent on Lipinski's standard of five. Conclusion: Genistein, Hesperidin, and epigallocatechin-3 are the potential ligands in regulating microtubule-related tau protein and Epigallocatechin-3 gallate is the most potent among them and the most elevated negative free vitality of official with the maximum interacting surface territory throughout docking studies.

scholarly journals A novel protein descriptor for the prediction of drug binding sites

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Mingjian Jiang ◽  
Zhen Li ◽  
Yujie Bian ◽  
Zhiqiang Wei
Keyword(s):  
Binding Site ◽  
Binding Sites ◽  
Three Dimensional ◽  
Drug Binding ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Site Prediction ◽  
Drug Binding Sites ◽  
Protein Descriptor ◽  
Novel Protein

Abstract Background Binding sites are the pockets of proteins that can bind drugs; the discovery of these pockets is a critical step in drug design. With the help of computers, protein pockets prediction can save manpower and financial resources. Results In this paper, a novel protein descriptor for the prediction of binding sites is proposed. Information on non-bonded interactions in the three-dimensional structure of a protein is captured by a combination of geometry-based and energy-based methods. Moreover, due to the rapid development of deep learning, all binding features are extracted to generate three-dimensional grids that are fed into a convolution neural network. Two datasets were introduced into the experiment. The sc-PDB dataset was used for descriptor extraction and binding site prediction, and the PDBbind dataset was used only for testing and verification of the generalization of the method. The comparison with previous methods shows that the proposed descriptor is effective in predicting the binding sites. Conclusions A new protein descriptor is proposed for the prediction of the drug binding sites of proteins. This method combines the three-dimensional structure of a protein and non-bonded interactions with small molecules to involve important factors influencing the formation of binding site. Analysis of the experiments indicates that the descriptor is robust for site prediction.

scholarly journals Species B adenovirus serotypes 3, 7, 11 and 35 share similar binding sites on the membrane cofactor protein CD46 receptor

2007 ◽  
Vol 88 (11) ◽  
pp. 2925-2934 ◽  
Author(s):  
Christoph Fleischli ◽  
Dominique Sirena ◽  
Guillaume Lesage ◽  
Menzo J. E. Havenga ◽  
Roberto Cattaneo ◽  
...  
Keyword(s):  
Binding Sites ◽  
Transgene Expression ◽  
Single Point ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Binding Surface ◽  
Short Consensus Repeat ◽  
Binding Residues ◽  
Necessary And Sufficient ◽  
Binding Determinants

We recently characterized the domains of the human cofactor protein CD46 involved in binding species B2 adenovirus (Ad) serotype 35. Here, the CD46 binding determinants are mapped for the species B1 Ad serotypes 3 and 7 and for the species B2 Ad11. Ad3, 7 and 11 bound and transduced CD46-positive rodent BHK cells at levels similar to Ad35. By using antibody-blocking experiments, hybrid CD46–CD4 receptor constructs and CD46 single point mutants, it is shown that Ad3, 7 and 11 share many of the Ad35-binding features on CD46. Both CD46 short consensus repeat domains SCR I and SCR II were necessary and sufficient for optimal binding and transgene expression, provided that they were positioned at an appropriate distance from the cell membrane. Similar to Ad35, most of the putative binding residues of Ad3, 7 and 11 were located on the same glycan-free, solvent-exposed face of the SCR I or SCR II domains, largely overlapping with the binding surface of the recently solved fiber knob Ad11–SCR I–II three-dimensional structure. Differences between species B1 and B2 Ads were documented with competition experiments based on anti-CD46 antibodies directed against epitopes flanking the putative Ad-binding sites, and with competition experiments based on soluble CD46 protein. It is concluded that the B1 and B2 species of Ad engage CD46 through similar binding surfaces.

scholarly journals Numerical and Experimental Study of Topographic Speed-Up Effects in Complex Terrain

Energies ◽  
2020 ◽  
Vol 13 (15) ◽  
pp. 3896 ◽  
Author(s):  
Takanori Uchida ◽  
Kenichiro Sugitani
Keyword(s):  
Wind Tunnel ◽  
Complex Terrain ◽  
Three Dimensional ◽  
Wind Tunnel Experiment ◽  
Dimensional Structure ◽  
Spanwise Direction ◽  
Two Dimensional ◽  
Wind Tunnel Experiments ◽  
Wire Probe ◽  
The Difference

Our research group is developing computational fluid dynamics (CFD)-based software for wind resource and energy production assessments in complex terrain called RIAM-COMPACT (Research Institute for Applied Mechanics, Kyushu University (RIAM)-Computational Prediction of Airflow over Complex Terrain), based on large eddy simulation (LES). In order to verify the prediction accuracy of RIAM-COMPACT, we conduct a wind tunnel experiment that uses a two-dimensional steep ridge model with a smooth surface. In the wind tunnel experiments, airflow measurements are performed using an I-type hot-wire probe and a split film probe that can detect forward and reverse flows. The results of the numerical simulation by LES are in better agreement with the wind tunnel experiment using the split film probe than the results of the wind tunnel experiment using the I-type hot wire probe. Furthermore, we calculate that the two-dimensional ridge model by changing the length in the spanwise direction, and discussed the instantaneous flow field and the time-averaged flow field for the three-dimensional structure of the flow behind the model. It was shown that the eddies in the downwind flow-separated region formed behind the two-dimensional ridge model were almost the same size in all cases, regardless of the difference in the length in the spanwise direction. In this study, we also perform a calculation with a varying inflow shear at the inflow boundary. It was clear that the size in the vortex region behind the model was almost the same in all the calculation results, regardless of the difference in the inflow shear. Next, we conduct wind tunnel experiments on complex terrain. In the wind tunnel experiments using a 1/2800 scale model, the effect of artificial irregularities on the terrain surface did not significantly appear on the airflow at the hub height of the wind turbine. On the other hand, in order to investigate the three-dimensional structure of the airflow in the swept area in detail, it was clearly shown that LES using a high-resolution computational grid is very effective.

scholarly journals Optical Response Characteristics of Single-Walled Carbon Nanotube Chirality Exposed to Oxidants with Different Oxidizing Power

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1091
Author(s):  
Yuji Matsukawa ◽  
Kazuo Umemura
Keyword(s):  
Near Infrared ◽  
Three Dimensional ◽  
Detection Sensitivity ◽  
Dimensional Structure ◽  
Single Walled Carbon ◽  
Response Characteristics ◽  
Oxidizing Power ◽  
Nir Absorption ◽  
The Difference ◽  
Walled Carbon Nanotubes

Semiconductor single-walled carbon nanotubes (SWNTs) have unique characteristics owing to differences in the three-dimensional structure (chirality) expressed by the chiral index (n,m), and many studies on the redox characteristics of chirality have been reported. In this study, we investigated the relationship between the chirality of SWNTs and the oxidizing power of oxidants by measuring the near-infrared (NIR) absorption spectra of two double-stranded DNA-SWNT complexes with the addition of three oxidants with different oxidizing powers. A dispersion was prepared by mixing 0.5 mg of SWNT powder with 1 mg/mL of DNA solution. Different concentrations of hydrogen peroxide (H2O2), potassium hexachloroidylate (IV) (K2IrCl6), or potassium permanganate (KMnO4) were added to the dispersion to induce oxidation. Thereafter, a catechin solution was added to observe if the absorbance of the oxidized dispersion was restored by the reducing action of the catechin. We found that the difference in the oxidizing power had a significant effect on the detection sensitivity of the chiralities of the SWNTs. Furthermore, we revealed a detectable range of oxidants with different oxidizing powers for each chirality.

scholarly journals Metal Binding Sites in Plant Soluble Inorganic Pyrophosphatases. An Example of the Use of ROSETTA Design and Hidden Markov Models to Guide the Homology Modeling of Proteins

2017 ◽  
Vol 56 (1) ◽  
Author(s):  
Luis Rosales-León Rosales-León ◽  
Eric Edmundo Hernández-Domínguez ◽  
Samantha Gaytán-Mondragón ◽  
Rogelio Rodríguez-Sotres
Keyword(s):  
Homology Modeling ◽  
Metal Binding ◽  
Binding Sites ◽  
In Silico ◽  
Markov Models ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Magnesium Ions ◽  
Three Dimensional Structure ◽  
Metal Binding Sites

In contrast to their counterparts in bacteria and animals the soluble inorganic pyrophosphatases from plant cells are active as monomers. The isoforms 1 and 4 from <em>Arabidopsis thaliana</em> have been characterized with more detail, but their three-dimensional structure is unavailable. Here, a recently published protocol (ROSETTA design-HMMer), is used to guide well-known techniques for homology-modeling, in the production of reliable models for the three-dimensional structure of these two arabidopsis isoforms. Their interaction with magnesium ions and pyrophosphate is analyzed <em>in silico</em>in silico.

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