Cdc25Mm is a mammalian Ras-specific guanine nucleotide exchange factor (GEF). By homology modeling we show that it shares with Sos-GEF the structure of the putative catalytic HI hairpin where the dominant negative T1184E mutation is located. Similarly to Cdc25MmT1184E, the isolated wild-type and mutant hairpins retain the ability to displace Ras-bound nucleotide, originate a stable Ras/GEF complex and downregulate the Ras pathway in vivo. These results indicate that nucleotide re-entry and Ras/GEF dissociation--final steps in the GEF catalytic cycle--require GEF regions different from the HI hairpin. GEF down-sizing could lead to development of novel Ras inhibitors.

Sacco, E., Fantinato, S., Manzoni, R., Metalli, D., DE GIOIA, L., Fantucci, P., et al. (2005). The isolated catalytic hairpin of the Ras-specific guanine nucleotide exchange factor Cdc25Mm retains nucleotide dissociation activity but has impaired nucleotide exchange activity. FEBS LETTERS, 579(30), 6851-6858 [10.1016/j.febslet.2005.11.024].

The isolated catalytic hairpin of the Ras-specific guanine nucleotide exchange factor Cdc25Mm retains nucleotide dissociation activity but has impaired nucleotide exchange activity

SACCO, ELENA;METALLI, DAVID;DE GIOIA, LUCA;FANTUCCI, PIERCARLO;ALBERGHINA, LILIA;VANONI, MARCO ERCOLE
2005

Abstract

Cdc25Mm is a mammalian Ras-specific guanine nucleotide exchange factor (GEF). By homology modeling we show that it shares with Sos-GEF the structure of the putative catalytic HI hairpin where the dominant negative T1184E mutation is located. Similarly to Cdc25MmT1184E, the isolated wild-type and mutant hairpins retain the ability to displace Ras-bound nucleotide, originate a stable Ras/GEF complex and downregulate the Ras pathway in vivo. These results indicate that nucleotide re-entry and Ras/GEF dissociation--final steps in the GEF catalytic cycle--require GEF regions different from the HI hairpin. GEF down-sizing could lead to development of novel Ras inhibitors.
Articolo in rivista - Articolo scientifico
Catalytic Domain; Genes, Dominant; Temperature; Catalysis; Anthranilic Acids; ras-GRF1; Cell Line, Transformed; Buffers; Genes, ras; Fibroblasts; Homozygote; Glutamic Acid; Cell Transformation, Neoplastic; Sequence Homology, Amino Acid; Mice; Molecular Sequence Data; Amino Acid Sequence; Genes, Reporter; Luciferases; Guanosine Diphosphate; Escherichia coli; Amino Acid Substitution; Protein Structure, Secondary; Down-Regulation; Animals; Models, Molecular; Guanosine Triphosphate; NIH 3T3 Cells; Crystallography, X-Ray
English
19-dic-2005
579
30
6851
6858
none
Sacco, E., Fantinato, S., Manzoni, R., Metalli, D., DE GIOIA, L., Fantucci, P., et al. (2005). The isolated catalytic hairpin of the Ras-specific guanine nucleotide exchange factor Cdc25Mm retains nucleotide dissociation activity but has impaired nucleotide exchange activity. FEBS LETTERS, 579(30), 6851-6858 [10.1016/j.febslet.2005.11.024].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/15396
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