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

Ligand Binding and Linkage00:49

Ligand Binding and Linkage

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 the...
Conserved Binding Sites01:49

Conserved Binding Sites

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 analyses the...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

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 pathway,...
Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...

You might also read

Related Articles

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

Sort by
Same author

The bonobo genome compared with the chimpanzee and human genomes.

Nature·2012
Same author

Evolutionary modeling of rate shifts reveals specificity determinants in HIV-1 subtypes.

PLoS computational biology·2008
Same author

Non-homogeneous models of sequence evolution in the Bio++ suite of libraries and programs.

BMC evolutionary biology·2008
Same author

Detecting groups of coevolving positions in a molecule: a clustering approach.

BMC evolutionary biology·2007
Same author

Bio++: a set of C++ libraries for sequence analysis, phylogenetics, molecular evolution and population genetics.

BMC bioinformatics·2006
Same author

A model-based approach for detecting coevolving positions in a molecule.

Molecular biology and evolution·2005

Related Experiment Video

Updated: Jul 2, 2026

Monitoring the Assembly of a Secreted Bacterial Virulence Factor Using Site-specific Crosslinking
11:33

Monitoring the Assembly of a Secreted Bacterial Virulence Factor Using Site-specific Crosslinking

Published on: December 17, 2013

Detecting site-specific biochemical constraints through substitution mapping.

Julien Dutheil1

  • 1Institut des Sciences de l'Evolution (UM2-CNRS), Université Montpellier 2, Place Eugène Bataillon, CC064, 34 095, Montpellier Cedex 5, France. jdutheil@daimi.au.dk

Journal of Molecular Evolution
|August 13, 2008
PubMed
Summary
This summary is machine-generated.

This study introduces a novel method to detect functionally important protein positions by analyzing evolutionary rates and specific biochemical properties. The approach identifies sites with conserved properties despite high overall evolutionary rates, offering new insights into protein evolution.

More Related Videos

Simultaneous Affinity Enrichment of Two Post-Translational Modifications for Quantification and Site Localization
12:11

Simultaneous Affinity Enrichment of Two Post-Translational Modifications for Quantification and Site Localization

Published on: February 27, 2020

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
07:08

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Published on: July 14, 2015

Related Experiment Videos

Last Updated: Jul 2, 2026

Monitoring the Assembly of a Secreted Bacterial Virulence Factor Using Site-specific Crosslinking
11:33

Monitoring the Assembly of a Secreted Bacterial Virulence Factor Using Site-specific Crosslinking

Published on: December 17, 2013

Simultaneous Affinity Enrichment of Two Post-Translational Modifications for Quantification and Site Localization
12:11

Simultaneous Affinity Enrichment of Two Post-Translational Modifications for Quantification and Site Localization

Published on: February 27, 2020

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
07:08

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Published on: July 14, 2015

Area of Science:

  • Molecular Evolution
  • Biochemistry
  • Bioinformatics

Background:

  • The neutral theory of molecular evolution posits that most mutations are neutral or deleterious.
  • Evolutionary rate at a protein position reflects functional/structural constraint.
  • Existing methods may miss constrained sites with high substitution rates if biochemical properties are conserved.

Purpose of the Study:

  • Introduce a new evolutionary rate measure considering biochemical properties (e.g., volume, polarity, charge).
  • Develop a statistical method to identify sites with conserved biochemical properties despite overall evolutionary rates.
  • Highlight advantages over single-rate methods: significance assessment, constraint type identification, and detection of novel sites.

Main Methods:

  • Developed a novel evolutionary rate measure incorporating biochemical property evolution.
  • Implemented a two-rate statistical comparison method to assess property-specific constraint.
  • Applied the method to a 200-sequence dataset of triosephosphate isomerase.

Main Results:

  • Identified significant cases of positions constrained for polarity, volume, or charge in triosephosphate isomerase.
  • Demonstrated that the two-rate method detects positions missed by traditional single-rate approaches.
  • Localized these constrained positions in the protein's three-dimensional structure.

Conclusions:

  • The new method enhances the detection of functionally and structurally important protein sites.
  • It provides deeper insights into the types of evolutionary constraints acting on specific positions.
  • Findings are relevant for both molecular evolutionists and biochemists studying protein function.