Page last updated: 2024-10-24

Atg8 activating enzyme activity

Definition

Target type: molecularfunction

Catalysis of the activation of the small ubiquitin-related modifier APG8, through the formation of an ATP-dependent high-energy thiolester bond. [GOC:mah]

Atg8 activating enzyme activity is a crucial step in the autophagy pathway, a cellular process responsible for degrading and recycling damaged organelles and proteins. This activity is catalyzed by an enzyme called Atg7, which plays a vital role in attaching the Atg8 protein to the autophagosomal membrane. The process starts with Atg7 activating Atg8 by first converting it into a high-energy thioester intermediate. This reaction involves the transfer of AMP from ATP to the carboxyl terminus of Atg8, generating Atg8-AMP. Next, Atg7 transfers the activated Atg8-AMP to the carboxyl terminus of phosphatidylethanolamine (PE), a lipid molecule present in the autophagosomal membrane. This process results in the formation of a covalent bond between Atg8 and PE, which anchors Atg8 to the autophagosomal membrane. This attachment of Atg8 to the membrane is essential for the formation of the autophagosome, the double-membrane vesicle that engulfs the cellular cargo destined for degradation. The Atg8 activating enzyme activity, therefore, plays a critical role in the initiation and progression of autophagy, enabling the efficient removal of damaged cellular components and maintaining cellular homeostasis.'
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Proteins (1)

ProteinDefinitionTaxonomy
Ubiquitin-like modifier-activating enzyme ATG7A ubiquitin-like modifier-activating enzyme ATG7 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O95352]Homo sapiens (human)

Compounds (1)

CompoundDefinitionClassesRoles
pevonedistatpevonedistat : A pyrrolopyrimidine that is 7H-pyrrolo[2,3-d]pyrimidine which is substituted by a (1S)-2,3-dihydro-1H-inden-1-ylnitrilo group at position 4 and by a (1S,3S,4S)-3-hydroxy-4-[(sulfamoyloxy)methyl]cyclopentyl group at position 7. It is a potent and selective NEDD8-activating enzyme inhibitor with an IC50 of 4.7 nM, and currently under clinical investigation for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes.

pevonedistat: a potent and selective inhibitor of NAE (NEDD8-activating enzyme)
cyclopentanols;
indanes;
pyrrolopyrimidine;
secondary amino compound;
sulfamidate
antineoplastic agent;
apoptosis inducer