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Structural analysis of protein Z gene variants in patients with foetal losses.
MedLine Citation:
PMID:  23846529     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 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.
Authors:
R Caliandro; G Nico; G Tiscia; G Favuzzi; V De Stefano; E Rossi; M Margaglione; E Grandone
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-7-11
Journal Detail:
Title:  Thrombosis and haemostasis     Volume:  110     ISSN:  0340-6245     ISO Abbreviation:  Thromb. Haemost.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-7-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7608063     Medline TA:  Thromb Haemost     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Elvira Grandone, MD, PhD, Atherosclerosis and Thrombosis Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza", S. Giovanni Rotondo, Foggia, Italy, Tel./Fax: +39 0 882 416273, E-mail: e.grandone@operapadrepio.it.
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