Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade

L Huang, E Kinnucan, G Wang, S Beaudenon… - Science, 1999 - science.org
L Huang, E Kinnucan, G Wang, S Beaudenon, PM Howley, JM Huibregtse, NP Pavletich
Science, 1999science.org
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 …
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.
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