Structure Determination and Dynamics of Peptides Overlapping the Catalytic Hairpin of the Ras-Specific GEF Cdc25Mm (Articolo in rivista)

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  • Structure Determination and Dynamics of Peptides Overlapping the Catalytic Hairpin of the Ras-Specific GEF Cdc25Mm (Articolo in rivista) (literal)
Anno
  • 2003-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1021/bi0344026 (literal)
Alternative label
  • Consonni R., Arosio I., Recca T., Longhi R., Colombo G., Vanoni M. (2003)
    Structure Determination and Dynamics of Peptides Overlapping the Catalytic Hairpin of the Ras-Specific GEF Cdc25Mm
    in Biochemistry (Easton)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Consonni R., Arosio I., Recca T., Longhi R., Colombo G., Vanoni M. (literal)
Pagina inizio
  • 12154 (literal)
Pagina fine
  • 12162 (literal)
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  • http://pubs.acs.org/doi/abs/10.1021/bi0344026 (literal)
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  • 42 (literal)
Rivista
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  • Articolo in pubblicazione internazionale (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Consonni R., Arosio I., Recca T. Istituo per lo Studio delle Macromolecole, CNR, Milano Longhi R., Colombo G. Istituto di Chimica del Riconoscimento Molecolare, CNR, Milano Vanoni M. Dip. Biotecnologie e Bioscienze, Univ. Milano-Bicocca, Milano (literal)
Titolo
  • Structure Determination and Dynamics of Peptides Overlapping the Catalytic Hairpin of the Ras-Specific GEF Cdc25Mm (literal)
Abstract
  • Ras proteins are small G proteins playing a major role in eukaryotic signal transduction. Guanine nucleotide exchange factors (GEF) stimulate GDP/GTP exchange, resulting in the formation of the active Ras-GTP complex. In mammalian cells, two major Ras-specific GEF exist: Sos-like and Cdc25-like. To date, structural data are available only for Cdc25Mm.We designed and synthesized Cdc25Mm-derived peptides spanning residues corresponding to the hSos1 HI helical hairpin that has been implicated in the GEF catalytic mechanism. NMR experiments on a chemically synthesized Cdc25Mm 1178-1222 peptide proved that helix I readily reaches a conformation very similar to the corresponding helix in hSos1, while residues corresponding to helix H in hSos1 show higher conformational flexibility. Molecular dynamics studies with the appropriate solvent model showed that different conformational spaces are available for the peptide. Since helix H is making several contacts with Ras and a Cdc25Mm 1178-1222 peptide is able to bind nucleotidefree Ras in a BIAcore assay, the peptide must be able to obtain the proper Ras-interacting conformation, at least transiently. These results indicate that rational design and improvement of the Ras-interacting peptides should take into account conformational and flexibility features to obtain molecules with the appropriate biochemical properties. (literal)
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