Structural analysis of protein Z gene variants in patients with foetal losses.
Thromb Haemost
; 110(3): 534-42, 2013 Sep.
Article
in En
| MEDLINE
| ID: mdl-23846529
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 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Blood Proteins
/
Abortion, Spontaneous
Type of study:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
/
Middle aged
Language:
En
Journal:
Thromb Haemost
Year:
2013
Document type:
Article