Heparin binding domain of antithrombin III: Characterization using a synthetic peptide directed polyclonal antibody

Journal Article · Tue Sep 25 04:00:00 EDT 1990 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00490a010· OSTI ID:5707724

Smith, J W; Dey, B; Knauer, D J ^[1]

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1. Univ. of California, Irvine (USA)

Antithrombin III (ATIII) is a plasma-borne serine protease inhibitor that apparently forms covalent complexes with thrombin. The interaction between ATIII and thrombin is enhanced several thousandfold by the glycosaminoglycan, heparin. The authors have previously proposed that the heparin binding site of ATIII residues within a region extending from amino acid residues 114-156. Computer-assisted analysis of this region revealed the presence of a 22 amino acid domain (residues 124-145), part of which shows a strong potential for the formation of an amphipathic helix: hydrophobic on one face and highly positively charged on the other. In the presence studies, polyclonal antisera were generated against a synthetic peptide corresponding to residues 124-145 in native human ATIII. Affinity-purified IgG from these antisera, as well as monovalent Fab's derived from them, specifically blocked the binding of heparin to ATIII. Additionally, occupancy of the heparin binding site by these same monovalent and bivalent IgG's at least partially substituted for heparin, accelerating linkage formation between ATIII and thrombin. These results provide the first immunological evidence that region 124-145 is directly involved in the binding of heparin to ATIII and that an antibody-induced conformational change within this region can mediate ATIII activation.

• OSTI ID: 5707724
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 29:38; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANTIBODIES
ANTICOAGULANTS
BETA DECAY RADIOISOTOPES
CARBOHYDRATES
CHEMICAL REACTIONS
COAGULANTS
CROSS-LINKING
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
HEMATOLOGIC AGENTS
HEMOSTATICS
HEPARIN
HYDROLASES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MONOCLONAL ANTIBODIES
MUCOPOLYSACCHARIDES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDE HYDROLASES
POLYMERIZATION
POLYSACCHARIDES
PURIFICATION
RADIOISOTOPES
RADIORECEPTOR ASSAY
SACCHARIDES
SERINE PROTEINASES
THROMBIN
TRACER TECHNIQUES