NAD+- protein-lysine ADP-ribosyltransferase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: L-lysyl-[protein] + NAD+ = H+ + N(6)-(ADP-D-ribosyl)-L-lysyl-[protein] + nicotinamide. [PMID:25043379, RHEA:58220]

NAD+-protein-lysine ADP-ribosyltransferase activity refers to the enzymatic process where an ADP-ribose moiety derived from nicotinamide adenine dinucleotide (NAD+) is transferred to a specific lysine residue on a target protein. This activity is catalyzed by a family of enzymes called ADP-ribosyltransferases (ARTs).

The molecular function of NAD+-protein-lysine ADP-ribosyltransferase activity involves the following steps:

1. **NAD+ Binding:** The enzyme binds NAD+ in its active site, typically through interactions with the adenine and nicotinamide moieties.
2. **Lysine Recognition:** The enzyme recognizes and interacts with the specific lysine residue on the target protein. This recognition can be influenced by the amino acid sequence surrounding the lysine residue and/or by structural features of the target protein.
3. **ADP-Ribosyl Transfer:** The enzyme catalyzes the transfer of the ADP-ribose moiety from NAD+ to the ε-amino group of the lysine residue on the target protein. This transfer reaction involves breaking the glycosidic bond between the nicotinamide and ribose moieties of NAD+, leaving a free nicotinamide molecule and an ADP-ribose moiety attached to the lysine residue.

The addition of ADP-ribose to a protein can significantly alter its function, typically by:

* **Altering Protein Activity:** ADP-ribosylation can either activate or inhibit the target protein's function, depending on the specific enzyme and target protein.
* **Modulating Protein-Protein Interactions:** ADP-ribosylation can change the conformation of the target protein and affect its ability to interact with other proteins.
* **Promoting Protein Degradation:** ADP-ribosylation can mark proteins for degradation by the proteasome, a cellular machinery responsible for removing damaged or unwanted proteins.

The molecular function of NAD+-protein-lysine ADP-ribosyltransferase activity is involved in a wide range of cellular processes, including signal transduction, DNA repair, cell cycle regulation, and immune response. Dysregulation of ADP-ribosyltransferase activity has been implicated in various human diseases, such as cancer, neurodegenerative disorders, and inflammatory diseases.'
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Proteins (5)

Compounds (24)