期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1990
卷号：87
期号：21
页码：8506-8510
DOI：10.1073/pnas.87.21.8506
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Glycosaminoglycans (GAGs) including heparin accelerate the inhibition of serine proteases by serine protease inhibitors (serpins), an essential process in regulating blood coagulation. to analyze the molecular basis for GAG recognition by the plasma serpin protein C inhibitor (PCI; also known as plasminogen activator inhibitor 3), we have constructed a complete, energy-minimized, three-dimensional model of PCI by using the structure of homologous alpha 1-antitrypsin as a template. Sequence analysis, hydrogen-bonding environment, and shape complementarity suggested that the N-terminal residues of PCI, which are not homologous to those of alpha 1-antitrypsin, form an amphipathic alpha-helix, here designated A+ since it precedes the alpha 1-antitrypsin A helix. Electrostatic calculations revealed a single, highly positive surface region arising from both the A+ and H helices, suggesting that this two-helix motif is required for GAG binding by PCI. The dominant role of electrostatic interactions in PCI-heparin binding was confirmed by the strong ionic strength dependence of heparin stimulation. The involvement of the A+ helix in heparin binding was verified by demonstrating that an anti-PCI antibody that specifically binds the A+ peptide blocks heparin binding.
