peptidyl-glutamate ADP-deribosylation

Definition

Target type: biologicalprocess

The removal of ADP-ribose from ADP-ribosylglutamate. [PMID:23481255]

Peptidyl-glutamate ADP-ribosylation is a post-translational modification (PTM) that involves the addition of an ADP-ribose moiety to the side chain of glutamate residues in proteins. This process is catalyzed by a specific family of enzymes known as ADP-ribosyltransferases (ARTs). The ADP-ribose donor is typically NAD+, which is hydrolyzed to nicotinamide and ADP-ribose during the reaction.

The ADP-ribose moiety can be attached to the glutamate side chain in a variety of ways, including mono-ADP-ribosylation, poly-ADP-ribosylation, and ADP-ribosylation of other PTMs such as ubiquitin. The specific type of ADP-ribosylation is determined by the specific ART involved.

Peptidyl-glutamate ADP-ribosylation plays a critical role in a wide range of cellular processes, including signal transduction, DNA repair, and inflammation. For example, ADP-ribosylation of proteins involved in the immune response can regulate the activity of immune cells and modulate the inflammatory response.

The biological significance of peptidyl-glutamate ADP-ribosylation is underscored by its involvement in a number of human diseases. For instance, dysregulation of ADP-ribosylation has been linked to cancer, neurodegenerative disorders, and autoimmune diseases.

The detailed mechanism of peptidyl-glutamate ADP-ribosylation involves the following steps:

1. **Substrate recognition:** The ART enzyme recognizes its target protein and binds to it via specific interactions with the glutamate residue that will be modified.

2. **NAD+ binding:** The ART enzyme binds to NAD+, which provides the ADP-ribose moiety that will be transferred to the target protein.

3. **ADP-ribosylation:** The ART enzyme catalyzes the transfer of the ADP-ribose moiety from NAD+ to the glutamate side chain of the target protein.

4. **Product release:** The ART enzyme releases the modified protein and the remaining NAD+ molecule.

Peptidyl-glutamate ADP-ribosylation is a dynamic process, and the level of ADP-ribosylation on a given protein can be regulated by various factors, including the activity of ARTs, the availability of NAD+, and the presence of specific protein interactors.

The study of peptidyl-glutamate ADP-ribosylation is a rapidly growing field, and ongoing research is providing new insights into the biological functions and implications of this important PTM. Understanding the mechanisms and regulation of this process has the potential to lead to the development of new therapeutic strategies for treating a variety of human diseases.'
"

Proteins (1)

Compounds (1)