Related Experiment Video
Updated: Jul 19, 2026
08:48
Specificity Analysis of Protein Lysine Methyltransferases Using SPOT Peptide Arrays
Published on: November 29, 2014
SET domain protein lysine methyltransferases: Structure, specificity and catalysis
1Department of Molecular Physiology and Biophysics, Mount Sinai School of Medicine, New York University, One Gustave L Levy Place, New York, NY 10029, USA.
Cellular and Molecular Life Sciences : CMLS
|October 3, 2006
Summary
Histone lysine methylation, regulated by SET domain proteins, is crucial for gene expression. Structural analysis of SET domains reveals key insights into the mechanism of histone methylation.
Area of Science:
- Biochemistry
- Epigenetics
- Structural Biology
Background:
- Histone lysine methylation is a key epigenetic mechanism controlling gene activity.
- SET domain-containing proteins catalyze this process, playing a fundamental role in eukaryotes.
- Understanding the structure of SET domains is essential for deciphering methylation regulation.
Purpose of the Study:
- To elucidate the three-dimensional structures of SET domains.
- To gain structural insights into histone lysine methylation.
- To understand the molecular basis of substrate specificity and catalytic mechanisms.
Main Methods:
- Determination of three-dimensional structures of SET domains.
- Analysis of SET domain structures in free state and bound to cofactor and histone peptide.
- Structural comparison to understand enzyme-cofactor-substrate interactions.
Main Results:
- The core SET domain structure features a two-domain architecture with a beta-barrel and a variable insert.
- An unusual knot-like structure forms the enzyme active site.
- Structures reveal insights into substrate specificity, methylation multiplicity, and catalytic mechanisms.
Conclusions:
- Structural data provides a molecular understanding of histone lysine methylation.
- The findings illuminate the catalytic mechanism and substrate recognition of SET domain enzymes.
- This research contributes to the fundamental knowledge of epigenetic regulation.
Related Concept Videos
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...
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
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...
02:54Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
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...
02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...