Carbon-Centered Radicals in Protein Manipulation.
Xuanxiao Chen1,2, Brian Josephson1, Benjamin G Davis1,2,3
1Department of Chemistry, University of Oxford, Oxford, OX1 3TA, U.K.
ACS Central Science
|May 1, 2023
Summary
New single electron/radical chemistry methods enable precise protein editing by forming C-C bonds. This approach offers versatile ways to create and study protein post-translational modifications (PTMs) for biological applications.
Area of Science:
- Chemical Biology
- Biochemistry
- Organic Chemistry
Background:
- Direct protein post-translational modification (PTM) methods are operationally simple but limited in altering C-C scaffolds.
- Traditional two-electron chemistry struggles with precise C-C bond construction in biological contexts.
Purpose of the Study:
- To review current methods for site-specific protein editing using single electron/radical chemistry.
- To highlight the potential of radical-mediated C-C bond formation for creating novel protein functions and PTMs.
Main Methods:
- Overview of radical chemistry approaches for protein modification.
- Discussion of selectivity for native or engineered residues.
- Analysis of radical generation strategies (on-protein, off-protein, photocatalysis).
Main Results:
- Single electron/radical chemistry enables precise "edits" to protein C-C scaffolds.
- Methods exploit native residues or engineered noncanonical side-chains.
- Compatibility with proteins and cells is a key consideration for applications.
Conclusions:
- Radical C-C bond formation on proteins is a rapidly advancing field in chemical biology.
- Despite technical hurdles, this approach holds significant potential for biological editing and PTM creation.
- Future applications in chemical biology are facilitated by these novel editing techniques.
More Related Videos
05:57Author Spotlight: In Silico Creation and Impact of Carbonylated Amino Acids on Protein Structure and Function
Published on: April 26, 2024
437
10:31Residue-Specific Exchange of Proline by Proline Analogs in Fluorescent Proteins: How "Molecular Surgery" of the Backbone Affects Folding and Stability
Published on: February 3, 2022
3.0K
Related Concept Videos
02:04Covalently Linked Protein Regulators
6.9K
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....
6.9K
02:26Conservation of Protein Domains Over Different Proteins
11.0K
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...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
11.0K
02:26Conservation of Protein Domains
3.1K
3.1K
01:24Tagging and Fusion Proteins
6.8K
Proteins are involved in several cellular processes and biochemical reactions. Analyzing a specific protein of interest requires it to be isolated from the other proteins in the cell. This is achieved by overexpressing the specific gene in a suitable host to produce large quantities of the target protein. A tag or label is recombined with the gene to produce a fusion protein containing the target protein and the tag. The tags on these fusion proteins can then be used for easy detection and...
6.8K
01:49Conserved Binding Sites
4.3K
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...
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...
4.3K
01:24Protein Organization
6.6K
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence....
The primary structure of a protein is its amino acid sequence....
6.6K