Details
- Autor(en) / Beteiligte
- Titel
- Rescue of the neuroblastoma mutant of the human nucleoside diphosphate kinase A/nm23-H1 by the natural osmolyte trimethylamine- N-oxide
- Ist Teil von
- FEBS letters, 2009-02, Vol.583 (4), p.820-824
- Ort / Verlag
- England: Elsevier B.V
- Erscheinungsjahr
- 2009
- Link zum Volltext
- Quelle
- Electronic Journals Library
- Beschreibungen/Notizen
- The point mutation S120G in human nucleoside diphosphate kinase A, identified in patients with neuroblastoma, causes a protein folding defect. The urea-unfolded protein cannot refold in vitro, and accumulates as a molten globule folding intermediate. We show here that the trimethylamine- N-oxide (TMAO) corrects the folding defect and stimulated subunit association. TMAO also substantially increased the stability to denaturation by urea of both wild-type and S120G mutant. A non-native folding intermediate accumulated in the presence of 4.5–7 M urea and of 2 M TMAO. It was inactive, monomeric, contained some secondary structure but no tertiary structure and displayed a remarkable stability to denaturation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0014-5793eISSN: 1873-3468DOI: 10.1016/j.febslet.2009.01.043Titel-ID: cdi_hal_primary_oai_HAL_hal_00358455v1
- Format
- –
- Schlagworte
- 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid, BisANS, Cellular Biology, Dose-Response Relationship, Drug, Folding intermediate, human nucleoside diphosphate kinase A (product of the nm23-H1 gene), Humans, K sv, K-pn, killer-of-prune, Kinetics, Life Sciences, Methylamines - metabolism, MG, Molten globule, NDPK-HA, Neoplasm Proteins - genetics, Neoplasm Proteins - metabolism, Neuroblastoma - genetics, Nm23, NM23 Nucleoside Diphosphate Kinases - genetics, NM23 Nucleoside Diphosphate Kinases - metabolism, Point Mutation, Protein Folding - drug effects, S120G mutant of the human NDPK-HA, S120G-NDPK-HA, the folding intermediate which accumulated in the presence of 4.5–7 M urea and 2 M TMAO, the molten globule folding intermediate previously described, the Stern–Volmer constant, TMAO, Trimethylamine- N-oxide, Urea - pharmacology