title: The N-terminal 1-16 peptide derived in vivo from protein seminal vesicle protein IV modulates alpha-thrombin activity: potential clinical implications.
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.
authors.affiliation: Dipartimento di Biochimica e Biofisica, Seconda Università degli Studi di Napoli,, Vico L. De Crecchio 7, 80138 Naples, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Lepretti
authors.forename: Susan
authors.initials: S
authors.lastname: Costantini
authors.forename: Gaetano
authors.initials: G
authors.lastname: Ammirato
authors.forename: Gaia
authors.initials: G
authors.lastname: Giuberti
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Facchiano
authors.forename: Salvatore
authors.initials: S
authors.lastname: Metafora
authors.forename: Paola
authors.initials: P
authors.lastname: Stiuso
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D002942:Circular Dichroism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D029607:Seminal Vesicle Secretory Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013917:Thrombin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D029607:Seminal Vesicle Secretory Proteins; D000990:Antithrombin III; D013917:Thrombin