The N-terminal 1-16 peptide derived in vivo from protein seminal vesicle protein IV modulates alpha-thrombin activity: potential clinical implications.
10.3858/emm.2008.40.5.541
- Author:
Marilena LEPRETTI
1
;
Susan COSTANTINI
;
Gaetano AMMIRATO
;
Gaia GIUBERTI
;
Michele CARAGLIA
;
Angelo M FACCHIANO
;
Salvatore METAFORA
;
Paola STIUSO
Author Information
1. Dipartimento di Biochimica e Biofisica, Seconda Universita degli Studi di Napoli, Vico L. De Crecchio 7, 80138 Naples, Italy. michele. caraglia@unina2.it
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
blood coagulation;
hemostasis;
Svp4 protein;
thrombin
- MeSH:
Amino Acid Sequence;
Animals;
Antithrombin III/metabolism;
Blood Coagulation/drug effects;
Circular Dichroism;
Humans;
Models, Molecular;
Molecular Sequence Data;
Peptide Fragments/*chemistry/pharmacology;
Protein Binding/drug effects;
Protein Structure, Secondary;
Protein Structure, Tertiary;
Rats;
Seminal Vesicle Secretory Proteins/*chemistry/genetics/metabolism;
Thrombin/*chemistry/genetics/metabolism
- From:Experimental & Molecular Medicine
2008;40(5):541-549
- CountryRepublic of Korea
- Language:English
-
Abstract:
We have previously shown that seminal vesicle protein IV (SV-IV) and its 1-70 N-terminal fragment have anti-inflammatory activity and modulate anti-thrombin III (AT) activity. Moreover, mass spectrometry analysis of purified SV-IV has shown that the protein was found to be highly heterogeneous and 14% of the total SV-IV molecules are truncated forms, of particular interest the 1-16, 1-17, and 1-18 peptides. In this work we report experimental data which demonstrate that the 1-16 peptide (P1-16) possesses a marked effect on the AT activity by preventing the formation of the thrombin-AT complex. We found that the formation of thrombin-AT complex is markedly decreased in the presence of P1-16 used at equimolar concentration with thrombin as evaluated with SDS-PAGE. We also monitored the conformational changes of thrombin in the presence of different P1-16 concentrations, and calculated the K(d) of thrombin/P1-16 system by circular dichroism technique. The probable interaction sites of P1-16 with thrombin have been also evaluated by molecular graphics and computational analyses. These results have potential implications in the treatment of sterility and thrombotic diseases.
