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Literature DB >> 26161728

Catalytically Important Residues of E6AP Ubiquitin Ligase Identified Using Acid-Cleavable Photo-Cross-Linkers.

Abstract

Inactivation of the E6AP E3 ubiquitin ligase (UBE3A gene) causes Angelman syndrome, while aberrant degradation of p53 by E6AP is implicated in cervical cancers. Herein, we describe the development of photo-cross-linkers to discover catalytic residues of E6AP. Using these cross-linkers, we identified covalent modifications of the E6AP catalytic cysteine and two lysines: Lys(847) and Lys(799). Lys(847) is required for the formation of Lys(48)-linked polyubiquitin chains, while the K799A E6AP mutant was more active at producing Lys(48)-linked polyubiquitin chains. Thus, opposing roles of Lys(799) and Lys(847) pave the path forward to pharmacological inhibitors or activators of E6AP for therapeutic purposes.

Entities: CellLine Chemical Disease Gene Mutation Species

Mesh：

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Year: 2015 PMID： 26161728 PMCID： PMC4527872 DOI： 10.1021/acs.biochem.5b00625

Source DB: PubMed Journal: Biochemistry ISSN： 0006-2960 Impact factor: 3.162

18 in total

1. Sequence determinants of E2-E6AP binding affinity and specificity.

Authors: Ziad M Eletr; Brian Kuhlman
Journal: J Mol Biol Date: 2007-03-19 Impact factor: 5.469

2. Gel-eluted liquid fraction entrapment electrophoresis: an electrophoretic method for broad molecular weight range proteome separation.

Authors: John C Tran; Alan A Doucette
Journal: Anal Chem Date: 2008-01-30 Impact factor: 6.986

3. Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1) and characterization of their interaction with E6-AP and RSP5.

Authors: U Nuber; S Schwarz; P Kaiser; R Schneider; M Scheffner
Journal: J Biol Chem Date: 1996-02-02 Impact factor: 5.157

Catalytically Important Residues of E6AP Ubiquitin Ligase Identified Using Acid-Cleavable Photo-Cross-Linkers.

1. Sequence determinants of E2-E6AP binding affinity and specificity.

2. Gel-eluted liquid fraction entrapment electrophoresis: an electrophoretic method for broad molecular weight range proteome separation.

3. Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1) and characterization of their interaction with E6-AP and RSP5.

4. Protein ubiquitination involving an E1-E2-E3 enzyme ubiquitin thioester cascade.

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

6. UBE3A/E6-AP mutations cause Angelman syndrome.

7. Photo-leucine incorporation reveals the target of a cyclodepsipeptide inhibitor of cotranslational translocation.

8. Conformational flexibility underlies ubiquitin ligation mediated by the WWP1 HECT domain E3 ligase.

9. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53.

10. Biochemical analysis of Angelman syndrome-associated mutations in the E3 ubiquitin ligase E6-associated protein.

1. Mapping low-affinity/high-specificity peptide-protein interactions using ligand-footprinting mass spectrometry.

Review 2. Decoding the messaging of the ubiquitin system using chemical and protein probes.

3. Photocrosslinking Activity-Based Probes for Ubiquitin RING E3 Ligases.