Rescue of the neuroblastoma mutant of the human nucleoside diphosphate kinase A/nm23‐H1 by the natural osmolyte trimethylamine‐ N ‐oxide | Zendy

Georgescauld Florian | Zendy; Mocan Iulia | Zendy; Lacombe Marie-Lise | Zendy; Lascu Ioan | Zendy

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Rescue of the neuroblastoma mutant of the human nucleoside diphosphate kinase A/nm23‐H1 by the natural osmolyte trimethylamine‐ N ‐oxide

Author(s) -

Georgescauld Florian,

Mocan Iulia,

Lacombe Marie-Lise,

Lascu Ioan

Publication year - 2009

Publication title -

febs letters

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.593

H-Index - 257

eISSN - 1873-3468

pISSN - 0014-5793

DOI - 10.1016/j.febslet.2009.01.043

Subject(s) - trimethylamine n oxide , chemistry , osmolyte , denaturation (fissile materials) , urea , biochemistry , mutant , protein folding , folding (dsp implementation) , trimethylamine , protein subunit , point mutation , biophysics , biology , nuclear chemistry , electrical engineering , gene , engineering

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.

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