Exp Mol Med.
2008 Oct;40(5):541-549. 10.3858/emm.2008.40.5.541.
The N-terminal 1-16 peptide derived in vivo from protein seminal vesicle protein IV modulates alpha-thrombin activity: potential clinical implications
- Affiliations
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- 1Dipartimento di Biochimica e Biofisica, Seconda Universita degli Studi di Napoli, Vico L. De Crecchio 7, 80138 Naples, Italy. michele. caraglia@unina2.it
- 2Laboratorio di Bioinformatica e Biologia Computazionale, Istituto di Scienze dell'Alimentazione, CNR Via Roma 52 A/C, 83100 Avellino, Italy.
- 3Centro di Ricerca Interdipartimentale di Scienze, Computazionali e Biotecnologiche (CRISCEB), Seconda Universita degli Studi di Napoli, Via Costantinopoli 16, 80138 Naples, Italy.
- KMID: 1104808
- DOI: http://doi.org/10.3858/emm.2008.40.5.541
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.
Keyword
MeSH Terms
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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
