Related Experiment Video
Updated: May 13, 2026
07:08
Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Functional site plasticity in domain superfamilies
Benoit H Dessailly1, Natalie L Dawson, Kenji Mizuguchi
1National Institute of Biomedical Innovation, Osaka, Japan.
Biochimica Et Biophysica Acta
|March 19, 2013
Summary
This study reveals significant functional site diversity within protein superfamilies, particularly for protein-protein interactions, highlighting protein plasticity and aiding systems biology research.
Area of Science:
- Structural biology
- Bioinformatics
- Protein science
Background:
- Understanding functional site diversity in homologous protein superfamilies is crucial for systems biology.
- Previous studies have indicated preferential locations for functional sites but lacked comprehensive quantitative analysis.
Purpose of the Study:
- To conduct the first quantitative analysis of functional site diversity across homologous domain superfamilies.
- To investigate the spatial plasticity of different functional site types (catalytic, small-ligand, protein-protein interfaces).
- To identify superfamilies with extreme functional site diversity and explore reasons for this plasticity.
Main Methods:
- Quantitative analysis of functional site diversity in homologous domain superfamilies.
- Separate consideration of different functional site types.
- Utilized a large dataset for comprehensive analysis.
Main Results:
- Most diverse superfamilies exhibit high plasticity in functional site locations, especially for protein-protein interfaces.
- Catalytic sites show limited topological locations, while small-ligand binding sites exhibit moderate diversity.
- Confirmed preferential locations of functional sites but emphasized the importance of considering diverse sites in large superfamilies.
- Identified superfamilies with extreme diversity, linked to structural plasticity.
Conclusions:
- Protein superfamilies display significant functional site diversity, challenging previous assumptions of strict site conservation.
- The plasticity of functional sites, particularly protein-protein interfaces, is a key feature in diverse superfamilies.
- Data accessibility via the CATH website aids further research in systems biology and protein interaction networks.
Related Concept Videos
01:49Conserved 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...
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...
01:49Conserved 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...
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...
00:49Ligand 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...
02:26Conservation of Protein Domains Over Different Proteins
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
01:19Allosteric 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,...
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,...
02:26Conservation of Protein Domains
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...