Predicted three-dimensional structure of the protease inhibitor domain of the Alzheimer's disease β-amyloid precursor

1991 ◽  
Vol 9 (1) ◽  
pp. 1-11 ◽  
Author(s):  
R. Scott Struthers ◽  
David H. Kitson ◽  
Arnold T. Hagler
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protease Inhibitor ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Β Amyloid

Computer-aided methods for 3-D visualization of serial sections and thick biological specimens

1992 ◽  
Vol 50 (2) ◽  
pp. 1060-1061
Author(s):  
Mark Ellisman ◽  
Maryann Martone ◽  
Gabriel Soto ◽  
Eleizer Masliah ◽  
David Hessler ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Three Dimensional ◽  
Neuritic Plaque ◽  
Dimensional Structure ◽  
Data Sets ◽  
Molecular Physiology ◽  
Research Activities ◽  
Computer Aided ◽  
Dimensional Reconstruction

Structurally-oriented biologists examine cells, tissues, organelles and macromolecules in order to gain insight into cellular and molecular physiology by relating structure to function. The understanding of these structures can be greatly enhanced by the use of techniques for the visualization and quantitative analysis of three-dimensional structure. Three projects from current research activities will be presented in order to illustrate both the present capabilities of computer aided techniques as well as their limitations and future possibilities.The first project concerns the three-dimensional reconstruction of the neuritic plaques found in the brains of patients with Alzheimer's disease. We have developed a software package “Synu” for investigation of 3D data sets which has been used in conjunction with laser confocal light microscopy to study the structure of the neuritic plaque. Tissue sections of autopsy samples from patients with Alzheimer's disease were double-labeled for tau, a cytoskeletal marker for abnormal neurites, and synaptophysin, a marker of presynaptic terminals.

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 ALZHEIMER’S DISEASE THERAPEUTIC APPROACHES

2018 ◽  
Vol 11 (7) ◽  
pp. 17
Author(s):  
Sandhya A ◽  
Gomathi Kannayiram
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Misfolding ◽  
Amyloid Fibrils ◽  
Adult Population ◽  
Three Dimensional ◽  
Lewy Bodies ◽  
Cerebral Hypoperfusion ◽  
Dimensional Structure ◽  
Islet Amyloid

A protein is a large biomolecule which consists of one or more chains of amino acid residues. Proteins exhibit a biological phenomenon in which, they are misfolded as aggregates (i.e., accumulate and clump together) either intra- or extracellularly. This process plays a central role in the pathogenesis of Alzheimer’s disease (AD) and diabetes mellitus (DM) - 2 and common for many degenerative diseases. In this case, the histopathological consequences of protein misfolding such as sensile plaques and neurofibrillary tangles in AD and lewy bodies in Parkinson’s disease occur. 8–10% of adult population shares risk factors with AD. Amyloid fibrils which build up in tissue as an abnormal protein form Amyloidosis. Conformational change in three-dimensional structure forms amyloid fibrils. Type 2 DM is characterized by the deposition of islet amyloid polypeptide within beta cells of the pancreas which leads to chronic cerebral hypoperfusion that result in degeneration of neuroglial cells.

scholarly journals Common structural features determine the effectiveness of carvedilol, daunomycin and rolitetracycline as inhibitors of Alzheimer β-amyloid fibril formation

1999 ◽  
Vol 343 (2) ◽  
pp. 419-423 ◽  
Author(s):  
David R. HOWLETT ◽  
Ashley R. GEORGE ◽  
Davina E. OWEN ◽  
Robin V. WARD ◽  
Roger E. MARKWELL
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuroblastoma Cell ◽  
Three Dimensional ◽  
Structural Features ◽  
Fibril Formation ◽  
Amyloid Peptide ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Β Amyloid

One of the major pathological features of Alzheimer's disease is the deposition of β-amyloid peptide (Aβ). Cellular toxicity has been shown to be associated with fibrillar forms of Aβ; preventing this fibril formation is therefore viewed as a possible method of slowing disease progression in Alzheimer's disease. With the use of a series of tetracyclic and carbazole-type compounds as inhibitors of Aβ fibril formation, we here describe a number of common structural features that seem to be associated with the inhibitory properties of these agents. Compounds such as carvedilol, rolitetracycline and daunomycin, which are shown to inhibit Aβ fibril formation, also prevent the formation of species of peptide that demonstrate biological activity in a human neuroblastoma cell line. Molecular modelling data suggest that these compounds have in common the ability to adopt a specific three-dimensional pharmacophore conformation that might be essential for binding to Aβ and preventing it from forming fibrils. Understanding such drug-peptide interactions might aid the development of disease-modifying agents.

The Three-dimensional structure of frozen-hydrated nudaurelia capensis β virus

1987 ◽  
Vol 45 ◽  
pp. 650-651
Author(s):  
N. H. Olson ◽  
T. S. Baker ◽  
Wu Bo Mu ◽  
J. E. Johnson ◽  
D. A. Hendry
Keyword(s):  
South African ◽  
Rna Virus ◽  
Carbon Film ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Electron Dose ◽  
Total Electron ◽  
Three Dimensional Structure ◽  
Negative Stain ◽  
Dimensional Reconstruction

Nudaurelia capensis β virus (NβV) is an RNA virus of the South African Pine Emperor moth, Nudaurelia cytherea capensis (Lepidoptera: Saturniidae). The NβV capsid is a T = 4 icosahedron that contains 60T = 240 subunits of the coat protein (Mr = 61,000). A three-dimensional reconstruction of the NβV capsid was previously computed from visions embedded in negative stain suspended over holes in a carbon film. We have re-examined the three-dimensional structure of NβV, using cryo-microscopy to examine the native, unstained structure of the virion and to provide a initial phasing model for high-resolution x-ray crystallographic studiesNβV was purified and prepared for cryo-microscopy as described. Micrographs were recorded ∼1 - 2 μm underfocus at a magnification of 49,000X with a total electron dose of about 1800 e-/nm2.

Three Dimensional structure and organization of diploid chromosomes by optical section microscopy

1987 ◽  
Vol 45 ◽  
pp. 633-635
Author(s):  
David A. Agard ◽  
Yasushi Hiraoka ◽  
John W. Sedat
Keyword(s):  
Dimensional Space ◽  
Three Dimensional ◽  
Developmental State ◽  
Mitotic Cell ◽  
Biological Properties ◽  
Dimensional Structure ◽  
Specific Gene ◽  
Three Dimensional Structure ◽  
Complementary Techniques ◽  
Dynamic Structures

In an effort to understand the complex relationship between structure and biological function within the nucleus, we have embarked on a program to examine the three-dimensional structure and organization of Drosophila melanogaster embryonic chromosomes. Our overall goal is to determine how DNA and proteins are organized into complex and highly dynamic structures (chromosomes) and how these chromosomes are arranged in three dimensional space within the cell nucleus. Futher, we hope to be able to correlate structual data with such fundamental biological properties as stage in the mitotic cell cycle, developmental state and transcription at specific gene loci.Towards this end, we have been developing methodologies for the three-dimensional analysis of non-crystalline biological specimens using optical and electron microscopy. We feel that the combination of these two complementary techniques allows an unprecedented look at the structural organization of cellular components ranging in size from 100A to 100 microns.

Three-Dimensional Structure of Cloned T3 Connector Protein at 1.6nm Resolution

1990 ◽  
Vol 48 (1) ◽  
pp. 282-283
Author(s):  
José L. Carrascosa ◽  
José M. Valpuesta ◽  
Hisao Fujisawa
Keyword(s):  
Dna Sequences ◽  
Expression Vector ◽  
Three Dimensional ◽  
Deae Cellulose ◽  
Dna Packaging ◽  
Dimensional Structure ◽  
Two Dimensional ◽  
Freezing And Thawing ◽  
Three Dimensional Structure ◽  
Dimensional Reconstruction

The head to tail connector of bacteriophages plays a fundamental role in the assembly of viral heads and DNA packaging. In spite of the absence of sequence homology, the structure of connectors from different viruses (T4, Ø29, T3, P22, etc) share common morphological features, that are most clearly revealed in their three-dimensional structure. We have studied the three-dimensional reconstruction of the connector protein from phage T3 (gp 8) from tilted view of two dimensional crystals obtained from this protein after cloning and purification.DNA sequences including gene 8 from phage T3 were cloned, into Bam Hl-Eco Rl sites down stream of lambda promotor PL, in the expression vector pNT45 under the control of cI857. E R204 (pNT89) cells were incubated at 42°C for 2h, harvested and resuspended in 20 mM Tris HC1 (pH 7.4), 7mM 2 mercaptoethanol, ImM EDTA. The cells were lysed by freezing and thawing in the presence of lysozyme (lmg/ml) and ligthly sonicated. The low speed supernatant was precipitated by ammonium sulfate (60% saturated) and dissolved in the original buffer to be subjected to gel nitration through Sepharose 6B, followed by phosphocellulose colum (Pll) and DEAE cellulose colum (DE52). Purified gp8 appeared at 0.3M NaCl and formed crystals when its concentration increased above 1.5 mg/ml.

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