Dissecting NGF interactions with TrkA and p75 receptors by structural and functional studies of an anti-NGF neutralizing antibody (Articolo in rivista)

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  • Dissecting NGF interactions with TrkA and p75 receptors by structural and functional studies of an anti-NGF neutralizing antibody (Articolo in rivista) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Alternative label
  • Covaceuszach S., Cassetta A., Konarev P. V., Gonfloni S., Ibañez C., Rudolph R., Svergun D.I., Lamba D., Cattaneo A. (2008)
    Dissecting NGF interactions with TrkA and p75 receptors by structural and functional studies of an anti-NGF neutralizing antibody
    in Journal of Molecular Biology
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Covaceuszach S., Cassetta A., Konarev P. V., Gonfloni S., Ibañez C., Rudolph R., Svergun D.I., Lamba D., Cattaneo A. (literal)
Pagina inizio
  • 881 (literal)
Pagina fine
  • 896 (literal)
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  • 381 (literal)
Rivista
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  • PG110 is a humanised alphaD11 antibody that binds to Nerve Growth Factor (NGF) with high affinity. NGF is the prototypical member of the family of neurotrophin growth factors, which are involved in the growth and survival of nervous tissue. PG110 prevents the interaction of NGF with both its receptors, the high-affinity receptor TrKA and the low affinity receptor p75. This interaction plays a key role in pain transduction mechanisms in the adult peripheral nervous system. PG110 does not cross-react with other neurotrophins and therefore is a highly specific function-blocking molecule that is able to neutralise NGF bioactivity, both in vitro and in vivo. The precursor to PG110, alphaD11, originated in Lay Line Genomics and after the program was acquired by PanGenetics a comprehensive CMC and preclinical development program was initiated. (literal)
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  • PubMe (literal)
  • Scopu (literal)
  • ISI Web of Science (WOS) (literal)
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  • Covaceuszach S.: Lay Line Genomics, Roma Cassetta A.: IC-CNR, Trieste Konarev P. V.: EMBL, Hamburg, Germany Gonfloni S. : Univ. Roma II, Roma Ibañez C. : Univ. Stockholm, Sweden Rudolph R.: Univ. Halle, Germany Svergun D.I., EMBL, Hamburg, Germany Lamba D.: IC-CNR, Trieste Cattaneo A. : SISSA, Trieste; EBRI, Roma (literal)
Titolo
  • Dissecting NGF interactions with TrkA and p75 receptors by structural and functional studies of an anti-NGF neutralizing antibody (literal)
Abstract
  • The anti-nerve growth factor (NGF) monoclonal antibody alphaD11 is a potent antagonist that neutralizes the biological functions of its antigen in vivo. NGF antagonism is expected to be a highly effective and safe therapeutic approach in many pain states. A comprehensive functional and structural analysis of alphaD11 monoclonal antibody was carried out, showing its ability to neutralize NGF binding to either tropomyosine receptor kinase A (TrkA) or p75 receptors. The 3-D structure of the alphaD11 Fab fragment was solved at 1.7 A resolution. A computational docking model of the alphaD11 Fab-NGF complex, based on epitope mapping using a pool of 44 NGF mutants and experimentally validated by small-angle X-ray scattering, provided the structural basis for identifying the residues involved in alphaD11 Fab binding. The present study pinpoints loop II of NGF to be an important structural determinant for NGF biological activity mediated by TrkA receptor. (literal)
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