Exploring the mechanism of inhibition of human telomerase by cysteine-reactive compounds
| Autor: | Evelyne Ségal-Bendirdjian, Daniel Dauzonne, Marie-Paule Teulade-Fichou, Vanessa Masson, Florent Dingli, Guillaume Kellermann, Damarys Loew, Sophie Bombard |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Models Molecular Telomerase Biophysics Biochemistry Mass Spectrometry law.invention 03 medical and health sciences Structure-Activity Relationship 0302 clinical medicine Protein Domains Structural Biology law Genetics Humans Telomerase reverse transcriptase Amino Acid Sequence Cysteine Molecular Biology chemistry.chemical_classification Binding Sites Molecular Structure Sequence Homology Amino Acid Mutagenesis RNA Cell Biology Recombinant Proteins 030104 developmental biology Enzyme chemistry 030220 oncology & carcinogenesis Recombinant DNA Reverse Transcriptase Inhibitors Function (biology) Protein Binding |
| Zdroj: | FEBS letters. 591(6) |
| ISSN: | 1873-3468 |
| Popis: | Telomerase is an almost universal cancer target that consists minimally of a core protein human telomerase reverse transcriptase (hTERT) and a RNA component human telomerase RNA (hTR). Some inhibitors of this enzyme are thought to function by the covalent binding to one or several cysteine residues; however, this inhibition mechanism has never been investigated because of the difficulty in producing telomerase. In this study, we use a recent method to produce recombinant hTERT to analyze the effect of cysteine-reactive inhibitors on telomerase. Using mass spectrometry and mutagenesis analysis, we identify several targeted residues in separated domains of the hTERT protein and show that cysteine-reactive reagents abolish the interaction with the CR4/5 region of hTR. |
| Databáze: | OpenAIRE |
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