Post-translational modifications (PTMs) are important components in signaling transductions, which affect the activity of proteins in signaling pathways. Phosphorylation is the most common PTM. The other PTMs include acetylation, methylation, glycosylation, lipidation, nitrosylation and ubiquitination.
In signaling pathways, proteins exist in two states: activated and inactivated, which are generally under the regulation PTMs. PTMs mediate signaling transductions during cell proliferation and differentiation, immune response, metabolism, apoptosis, etc. Any dysregulation of PTMs in the cells leads to different levels of functional failures. Thus, learning how protein PTMs modulate signaling pathways are of great importance.
CD BioSciences offers a complete portfolio of solutions for resolve PTM-related issues including PTM profiling, substrate and enzyme identification and inhibitor/activator screening.
Protein phosphorylation is the most common reversible PTM, where a phosphoryl group is attached to a protein on Ser, Thr or Tyr. Kinases catalyze phosphorylation, while phosphatases catalyze dephosphorylation, in which a phosphoryl group is removed from a protein.
Protein phosphorylation often leads to structural changes which then affect protein functions by modulating protein folding, substrate affinity, stability, localization and activity. Notably, the majority of oncogenes identified so far are protein kinases, whose activity when dysregulated is related to the development of cancers.
See our solutions for Kinases & Phosphatases.
Acetylation is one of the major protein PTMs in cells, where an acetyl group from acetyl coenzyme A (acetyl-CoA) is transferred to a polypeptide chain. Acetyltransferases catalyze acetylation, while deacetylases catalyze deacetylation, in which an acetyl group is removed from a protein.
Like phosphorylation, acetylation also affects protein function by altering the properties of proteins such as hydrophobicity, solubility, protein conformation and affinity with other macromolecules. Consequently, dysregulation of acetylation can lead to metabolic disorders, cancers, neurodegeneration, and cardiovascular diseases.
See our solutions for Acetyltransferases & Deacetylases.
Ubiquitination is a PTM process, where ubiquitin is added to a lysine/cysteine/ serine/threonine of a substrate protein via the C-terminal glycine of ubiquitin. It is essential for balancing numerous physiological processes, through altering proteins' degradation, cellular location, activity, and interactions with other molecules to regulate protein functions in relevant signaling pathways.
Ubiquitination is catalyzed by E1, E2 and E3 enzymes, while deubiquitination is catalyzed by DUBs. Ubiquitination has been implicated in the pathogenesis of a variety of diseases and disorders such as neurodegenerative diseases, infection and immunity related diseases and cancers.
See our solutions for Ubiquitin Enzymes & DUBs.
Other PTMs and Their Enzymes
Protein glycosylation is one of the major PTM, where a carbohydrate is attached to a protein by a complex series of enzymatic steps. It affects protein folding, conformation, location, stability and activity. As changes in glycosylation can modulate inflammatory responses, glycosylation can be used to optimize the performance of therapeutic antibodies.
There are several types of enzymatic glycosylation: N-linked glycosylation, O-linked glycosylation, phosphoglycosylation, C-mannosylation, glypiation. Currently, at least 16 enzymes are involved in the formation of sugar-amino acid linkage.
S-nitrosylation is a rapid reversible, precisely targeted and redox-based PTM, where a nitric oxide group (-NO) is attached to cysteine in a protein to form an S-nitrosothiol (SNO). Dysregulation of S-nitrosylation is associated with diseases such as heart disease, neurodegenerative diseases (e.g., Parkinson's and Alzheimer's disease), Amyotrophic Lateral Sclerosis (ALS) and cancers.
Three classes of enzymes (S-nitrosylases) operate in order to conjugate -NO to proteins, which are analogous to ubiquitin enzymes (E1, E2 and E3).
Protein methylation is a type of PTM, where a one-carbon methyl group is attached to a protein on nitrogen-containing side-chains of arginine and lysine, or at the amino- and carboxy-termini. The methylation of histone epigenetically regulates gene expression, so does DNA methylation (e.g. m6A), which has become a hot research area recently.
S-adenosyl methionine (SAM) is the primary methyl group donor. Methyltransferases transfer methyl groups to target proteins, while demethylases catalyze the removal of methyl groups. These two processes are referred to as methylation and demethylation, respectively.
Solutions for PTM Study
Our solutions for PTMs include but is not limited to the following:
- N-linked glycosylation
- O-linked glycosylation
- Pyrrolidone carboxylic acid
- Profiling global protein post-translational modifications in a system (cells, tissues, etc).
- Detecting post-translational modifications of proteins in specific signaling pathways.
- Comparing post-translational modification levels in different conditions.
- Identifying substrate proteins for a certain post-translational modification.
- Determining the PTM sites on substrates.
- Identifying PTM enzymes for your substrates.
- Determining function domain or catalytic site on PTM enzymes.
- Analyzing the structures of PTM enzymes.
- Screening for inhibitors/activators for PTM enzymes.
- Determining the thermodynamic parameters of the interactions.
CD BioSciences offers cost-effect, high quality and hassle-free PTM enzymes related solutions to our clients worldwide. We guarantee to deliver our products and results on time. Please feel free to contact us.
For research use only. Not intended for any clinical use.