NEDD8 conjugating enzyme activity

Definition

Target type: molecularfunction

Isoenergetic transfer of NEDD8 from one protein to another via the reaction X-NEDD8 + Y = Y-NEDD8 + X, where both the X-NEDD8 and Y-NEDD8 linkages are thioester bonds between the C-terminal amino acid of NEDD8 and a sulfhydryl side group of a cysteine residue. [GOC:dph]

NEDD8 conjugating enzyme activity, also known as E2 activity for NEDD8, is a critical step in the NEDDylation pathway, a ubiquitin-like protein modification that regulates a wide range of cellular processes. This enzymatic activity involves the covalent attachment of NEDD8, a ubiquitin-like protein, to a target protein, typically a lysine residue within the target's consensus motif. The process is catalyzed by a three-enzyme cascade: 1) NEDD8 is activated by the E1 enzyme, an ATP-dependent ligase. 2) The activated NEDD8 is transferred to the E2 enzyme, the NEDD8 conjugating enzyme. 3) Finally, the E3 ligase recognizes the target protein and facilitates the transfer of NEDD8 from the E2 enzyme to the target protein. NEDD8 conjugating enzymes play a vital role in regulating the activity of many cellular proteins, including those involved in DNA replication, cell cycle progression, signal transduction, and protein degradation. The precise molecular mechanism of NEDD8 conjugation involves the formation of a thioester bond between the C-terminal glycine residue of NEDD8 and a cysteine residue within the active site of the E2 enzyme. This thioester intermediate is then transferred to the target protein, resulting in the formation of an isopeptide bond between NEDD8 and the target protein. The E2 enzyme can also interact with various E3 ligases, which provide substrate specificity and ensure the efficient and selective NEDDylation of specific target proteins. Mutations or dysregulation of NEDD8 conjugating enzyme activity have been implicated in various diseases, including cancer, neurodegenerative disorders, and inflammatory diseases. Thus, understanding the molecular function of NEDD8 conjugating enzymes is essential for developing therapeutic strategies for these diseases.'
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Proteins (1)

Compounds (1)