Structural analysis of protein Z gene variants in patients with foetal losses (Articolo in rivista)

Type
Label
  • Structural analysis of protein Z gene variants in patients with foetal losses (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1160/TH13-01-0005 (literal)
Alternative label
  • Caliandro, Rocco; Nico, Giovanni; Tiscia, Giovanni; Favuzzi, Giovanni; De Stefano, Valerio; Rossi, Elena; Margaglione, Maurizio; Grandone, Elvira (2013)
    Structural analysis of protein Z gene variants in patients with foetal losses
    in Thrombosis and haemostasis
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Caliandro, Rocco; Nico, Giovanni; Tiscia, Giovanni; Favuzzi, Giovanni; De Stefano, Valerio; Rossi, Elena; Margaglione, Maurizio; Grandone, Elvira (literal)
Pagina inizio
  • 534 (literal)
Pagina fine
  • 542 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 110 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 9 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 3 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Consiglio Nazionale delle Ricerche (CNR); Consiglio Nazionale delle Ricerche (CNR); IRCCS Casa Sollievo della Sofferenza S Giovanni R; Catholic University of the Sacred Heart; University of Foggia (literal)
Titolo
  • Structural analysis of protein Z gene variants in patients with foetal losses (literal)
Abstract
  • The role of protein Z (PZ) in the etiology of human disorders is unclear. A number of PZ gene variants, sporadic or polymorphic and found exclusively in the serine protease domain, have been observed. Crystal structures of PZ in complex with the PZ-dependent inhibitor (PZI) have been recently obtained. The aim of this study was a structural investigation of the serine protease PZ domain, aiming at finding common traits across disease-linked mutations. We performed 10-20 ns molecular dynamics for each of the observed PZ mutants to investigate their structure in aqueous solution. Simulation data were processed by novel tools to analyse the residue-by-residue backbone flexibility. Results showed that sporadic mutations are associated with anomalous flexibility of residues belonging to specific regions. Among them, the most important is a loop region which is in contact with the longest I helix of PZI. Other regions have been identified, which hold anomalous flexibility associated with potentially protective gene variants. In conclusion, a possible interpretation of effects associated with observed gene variants is provided. The exploration of PZ/PZI interactions seems essential in explaining these effects. (literal)
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