Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

5.9K
Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.9K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

4.9K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.9K
Amyloid Fibrils03:03

Amyloid Fibrils

9.9K
Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining,...
9.9K
Conserved Binding Sites01:49

Conserved Binding Sites

4.4K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.4K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

COMPASS: A Computational Pipeline to Identify Linkers Predicting Ubiquitinable PROTAC-Induced Ternary Complexes.

ChemMedChem·2026
Same author

Comparative biodegradation of functionalized graphene oxide nanosheets by myeloperoxidase and neutrophil extracellular traps.

Frontiers in bioengineering and biotechnology·2026
Same author

AcTor, a novel mTOR stimulator, potentiates ixazomib for the treatment of acute myeloid leukemia.

Molecular cancer·2026
Same author

AcTor, a novel mTOR stimulator, potentiates ixazomib for the treatment of acute myeloid leukemia.

Research square·2026
Same author

Quantifying loss of cell viability or adhesion using methylene blue.

Methods in cell biology·2026
Same author

Heat shock protein 10 as a chaperone modulating α-synuclein amyloid fibril formation.

Protein science : a publication of the Protein Society·2026

Related Experiment Video

Updated: Sep 18, 2025

Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time
07:56

Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time

Published on: May 30, 2021

3.3K

In silico identification of substrate-binding sites in type-1A α-synuclein amyloids.

Shraddha Parate1, Fiamma Buratti1, Leif A Eriksson2

  • 1Department of Life Sciences, Chalmers University of Technology, Göteborg, Sweden.

Biophysical Journal
|June 20, 2025
PubMed
Summary

Pathological amyloids, like those in Parkinson's and Alzheimer's, can catalyze reactions. Computational studies reveal a specific binding site on alpha-synuclein amyloid fibrils for small molecules like para-nitrophenyl phosphate.

More Related Videos

Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry for the Study of Alpha-Synuclein Structural Dynamics Under Physiological Conditions
08:40

Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry for the Study of Alpha-Synuclein Structural Dynamics Under Physiological Conditions

Published on: June 23, 2022

3.0K
Novel Atomic Force Microscopy Based Biopanning for Isolation of Morphology Specific Reagents against TDP-43 Variants in Amyotrophic Lateral Sclerosis
13:31

Novel Atomic Force Microscopy Based Biopanning for Isolation of Morphology Specific Reagents against TDP-43 Variants in Amyotrophic Lateral Sclerosis

Published on: February 12, 2015

8.9K

Related Experiment Videos

Last Updated: Sep 18, 2025

Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time
07:56

Utilizing Time-Resolved Protein-Induced Fluorescence Enhancement to Identify Stable Local Conformations One α-Synuclein Monomer at a Time

Published on: May 30, 2021

3.3K
Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry for the Study of Alpha-Synuclein Structural Dynamics Under Physiological Conditions
08:40

Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry for the Study of Alpha-Synuclein Structural Dynamics Under Physiological Conditions

Published on: June 23, 2022

3.0K
Novel Atomic Force Microscopy Based Biopanning for Isolation of Morphology Specific Reagents against TDP-43 Variants in Amyotrophic Lateral Sclerosis
13:31

Novel Atomic Force Microscopy Based Biopanning for Isolation of Morphology Specific Reagents against TDP-43 Variants in Amyotrophic Lateral Sclerosis

Published on: February 12, 2015

8.9K

Area of Science:

  • Biochemistry
  • Computational Biology
  • Neuroscience

Background:

  • Pathological amyloid fibrils in neurodegenerative diseases (e.g., Parkinson's, Alzheimer's) exhibit catalytic activity in vitro.
  • Understanding substrate interactions with amyloid structures is crucial for elucidating disease mechanisms.

Purpose of the Study:

  • To computationally investigate the interaction between small-molecule substrates and alpha-synuclein amyloid fibrils.
  • To identify and characterize substrate-binding sites on type-1A alpha-synuclein amyloid structures.

Main Methods:

  • Computational approaches including binding pocket prediction and molecular docking.
  • Simulation of para-nitrophenyl phosphate (pNPP) binding to identified sites.
  • Validation using 100 ns molecular dynamics simulations.

Main Results:

  • Three distinct substrate-binding sites were identified on the dimeric type-1A alpha-synuclein amyloid structure.
  • Molecular docking and dynamics simulations showed a preference for a specific site (Site 2) for pNPP.
  • Site 2 is located at the protofilament interface, rich in lysine and histidine-50, facilitating stable substrate interactions.

Conclusions:

  • The study provides molecular-level insights into the interaction between pNPP and a specific alpha-synuclein amyloid polymorph.
  • The identified binding site (Site 2) offers a mechanistic explanation for the observed catalytic activity.
  • This framework can be extended to study other substrates and amyloid structures.