Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade.
The E6AP ubiquitin-protein ligase (E3) mediates the human papillomavirus-induced degradation of the p53 tumor suppressor in cervical cancer and is mutated in Angelman syndrome, a neurological disorder. The crystal structure of the catalytic hect domain of E6AP reveals a bilobal structure with a broad catalytic cleft at the junction of ... the two lobes. The cleft consists of conserved residues whose mutation interferes with ubiquitin-thioester bond formation and is the site of Angelman syndrome mutations. The crystal structure of the E6AP hect domain bound to the UbcH7 ubiquitin-conjugating enzyme (E2) reveals the determinants of E2-E3 specificity and provides insights into the transfer of ubiquitin from the E2 to the E3.
Mesh Terms:
Amino Acid Sequence, Angelman Syndrome, Binding Sites, Catalytic Domain, Conserved Sequence, Crystallography, X-Ray, Cysteine, Humans, Ligases, Models, Molecular, Molecular Sequence Data, Mutation, Protein Conformation, Protein Structure, Secondary, Substrate Specificity, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Ubiquitins
Amino Acid Sequence, Angelman Syndrome, Binding Sites, Catalytic Domain, Conserved Sequence, Crystallography, X-Ray, Cysteine, Humans, Ligases, Models, Molecular, Molecular Sequence Data, Mutation, Protein Conformation, Protein Structure, Secondary, Substrate Specificity, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Ubiquitins
Science
Date: Nov. 12, 1999
PubMed ID: 10558980
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