Page last updated: 2024-10-24

NEDD8 ligase activity

Definition

Target type: molecularfunction

Catalysis of the transfer of NEDD8 to a substrate protein via the reaction X-NEDD8 + S = X + S-NEDD8, where X is either an E2 or E3 enzyme, the X-NEDD8 linkage is a thioester bond, and the S-NEDD8 linkage is an isopeptide bond between the C-terminal amino acid of NEDD8 and the epsilon-amino group of lysine residues in the substrate. [GOC:dph]

NEDD8 ligase activity is a critical molecular function involved in the post-translational modification of target proteins with the ubiquitin-like protein NEDD8. This process, known as NEDDylation, is essential for regulating a wide array of cellular processes, including signal transduction, DNA replication, cell cycle progression, and protein degradation. NEDD8 ligases, also known as E3 ligases, specifically recognize and bind to target proteins, facilitating the transfer of NEDD8 from a carrier protein (E2) to a lysine residue on the target protein. The NEDD8 ligase complex typically consists of a catalytic subunit, which possesses the enzymatic activity for NEDD8 conjugation, and a substrate recognition subunit, which determines the specificity of the ligase for particular target proteins. NEDDylation often modulates the activity and stability of target proteins, influencing their interactions with other proteins and their localization within the cell. Disruption of NEDDylation can have significant consequences for cellular function and can contribute to the development of various diseases, including cancer, neurodegenerative disorders, and immune dysfunction. The molecular function of NEDD8 ligase activity plays a crucial role in maintaining cellular homeostasis and ensuring proper regulation of key cellular processes.'
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Proteins (1)

ProteinDefinitionTaxonomy
E3 ubiquitin-protein ligase Mdm2An E3 ubiquitin-protein ligase Mdm2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q00987]Homo sapiens (human)

Compounds (19)

CompoundDefinitionClassesRoles
catecholcatecholsallelochemical;
genotoxin;
plant metabolite
gossypolGossypol: A dimeric sesquiterpene found in cottonseed (GOSSYPIUM). The (-) isomer is active as a male contraceptive (CONTRACEPTIVE AGENTS, MALE) whereas toxic symptoms are associated with the (+) isomer.
quinone1,4-benzoquinone : The simplest member of the class of 1,4-benzoquinones, obtained by the formal oxidation of hydroquinone to the corresponding diketone. It is a metabolite of benzene.

benzoquinone : The simplest members of the class of benzoquinones, consisting of cyclohexadiene which is substituted by two oxo groups.

quinone : Compounds having a fully conjugated cyclic dione structure, such as that of benzoquinones, derived from aromatic compounds by conversion of an even number of -CH= groups into -C(=O)- groups with any necessary rearrangement of double bonds (polycyclic and heterocyclic analogues are included).
1,4-benzoquinonescofactor;
human xenobiotic metabolite;
mouse metabolite
vorinostatvorinostat : A dicarboxylic acid diamide comprising suberic (octanedioic) acid coupled to aniline and hydroxylamine. A histone deacetylase inhibitor, it is marketed under the name Zolinza for the treatment of cutaneous T cell lymphoma (CTCL).

Vorinostat: A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME.
dicarboxylic acid diamide;
hydroxamic acid
antineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor
apomorphineApomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.aporphine alkaloidalpha-adrenergic drug;
antidyskinesia agent;
antiparkinson drug;
dopamine agonist;
emetic;
serotonergic drug
cytarabinebeta-D-arabinoside;
monosaccharide derivative;
pyrimidine nucleoside
antimetabolite;
antineoplastic agent;
antiviral agent;
immunosuppressive agent
nutlin 3stilbenoid
nutlin 2
nutlin 1nutlin 1: an MDM2 antagonist; structure in first source
nutlin-3anutlin 3: an MDM2 antagonist; structure in first sourcestilbenoid
MI-63MI-63 : An azaspiro compound resulting from the formal fusion of position 3 of 6-chloro-oxindole with position 3 of (2R,3SS5S)-3-(3-chloro-2-fluorophenyl)-5-(2,2-dimethylpropyl)-N-[2-(morpholin-4-yl)ethyl]pyrrolidine-2-carboxamide. It is a potent inhibitor of the MDM2-p53 interaction.azaspiro compound;
monochlorobenzenes;
monofluorobenzenes;
morpholines;
oxindoles;
pyrrolidines;
secondary carboxamide
apoptosis inducer
nutlin-3bNutlin;
piperazinone
anticoronaviral agent
pb 12
spautin-1
nvp-cgm097NVP-CGM097: an MDM2 and HDM2 inhibitor; structure in first source
rg7388RG7388: structure in first source
sar405838SAR405838: an inhibitor of the interaction of MDM2 and p53; has antineoplastic activity; structure in first source
rg7112
amg 232