Structure of an E6AP-UbcH7 complex: Insights into ubiquitination by the E2-E3 enzyme cascade Journal Article
| Authors: | Huang, L.; Kinnucan, E.; Wang, G.; Beaudenon, S.; Howley, P. M.; Huibregtse, J. M.; Pavletich, N. P. |
| Article Title: | Structure of an E6AP-UbcH7 complex: Insights into ubiquitination by the E2-E3 enzyme cascade |
| Abstract: | 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 deft at the junction of the two lobes. The deft 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. |
| Keywords: | gene mutation; mutation; protein conformation; protein domain; ubiquitin protein ligase; protein p53; amino acid sequence; conserved sequence; molecular sequence data; enzyme analysis; uterine cervix cancer; substrate specificity; models, molecular; crystallography, x-ray; binding sites; enzyme specificity; enzyme binding; enzyme structure; ubiquitin-conjugating enzymes; catalytic domain; ubiquitin-protein ligases; protein structure, secondary; cysteine; enzyme active site; ubiquitins; ubiquitin conjugating enzyme; ligases; humans; priority journal; article; happy puppet syndrome; angelman syndrome |
| Journal Title: | Science |
| Volume: | 286 |
| Issue: | 5443 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 1999-11-12 |
| Start Page: | 1321 |
| End Page: | 1326 |
| Language: | English |
| DOI: | 10.1126/science.286.5443.1321 |
| PUBMED: | 10558980 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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