Structural requirements of human tissue factor pathway inhibitor (TFPI) and heparin for TFPI-heparin interaction.
Heparin affinity chromatography of synthetic peptide fragments mimicking tissue factor pathway inhibitor (TFPI) indicated that the minimal heparin binding sequence consists of 12 amino acid residues located at the C-terminal tail. Within this minimal sequence, Arg-257 and Arg-259 appeared to contribute most significantly to interaction with heparin. Affinity chromatography of TFPI using immobilized heparin derivatives regiospecifically desulfated at O-6 of the glucosamine residue, N-2 of the glucosamine residue, and/or O-2 of the iduronic acid residue indicated that all the sulfate groups in heparin appeared to be required for TFPI-heparin interaction. Among them, however, the 6-O-sulfate groups appeared to make the largest contribution to the interaction, while the 2-O-sulfate groups contributed the least. In vitro experiments on the inhibition of factor Xa by TFPI enhanced with native and chemically modified heparins afforded similar results.
Department of Chemistry and Materials Technology, Faculty of Engineering and Design, Kyoto Institute of Technology, Japan.
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Ye
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Takano
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Hayashi
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Kato
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Kamikubo
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Nakahara
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Kumeda
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Hara
D000595:Amino Acid Sequence; D001665:Binding Sites; D001777:Blood Coagulation; D006493:Heparin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017421:Sequence Analysis
D008074:Lipoproteins; D010446:Peptide Fragments; C051928:lipoprotein-associated coagulation inhibitor; D006493:Heparin