1986 Fiscal Year Final Research Report Summary
Studies on Molecular Abnormality of Blood Coagulation and Fibrinolytic Factors
| Project/Area Number |
60480497
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
物質生物化学
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| Research Institution | Kyushu University |
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Principal Investigator |
IWANAGA Sadaaki Faculty of Science, Kyushu University, Professor, 理学部, 教授 (90029942)
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| Co-Investigator(Kenkyū-buntansha) |
MIYATA Toshiyuki Faculty of Science, Kyushu University, Instructor, 理学部, 助手 (90183970)
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| Project Period (FY) |
1985 – 1986
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| Keywords | Fibrinogen / Prothrombin / Abnormal molecule / Blood coagulation factor / セリンプロテアーゼ前駆体 |
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| Research Abstract |
(1) DEFECTIVE RELEASE OF FIBRINOPEPTIDE A DUE TO SUBSTITUTION OF A <alpha> ARGININE-16 BY CYSTEINE IN TWO ABNORMAL FIBRINOGENS KAWAGUCHI AND OSAKA: The propositi of two abnormal fibrinogens, designated as fibrinogen Kawaguchi and fibrinogen Osaka, are both heterozygotes for the abnormality of fibrinogen characterized by defective release of fibrinopeptide A (FPA). By employing a new strategy of utilizing lysyl endopeptidase, a seryl protease derived from Achromobacter lyticus M497-1, we separated aberrant A <alpha> 1-29 peptides from the digests of the S-pyridylethylated A <alpha> chain and identified substituion of A <alpha> Arg-16 by Cys in both abnormal fibrinogens Kawaguchi and Osaka.
(2) PROTHROMBIN TOKUSHIMA: A REPLACEMENT OF ARGININE-418 BY TRYPTOPHAN THAT IMPAIRS THE FIBRINOGEN CLOTTING ACTIVITY OF DERIVED THROMBIN TOKUSHIMA; Structural studies on a hereditarily abnormal prothrombin, prothrombin Tokushima, have been performed to identify the difference responsible for its reduced fibrinogen clotting activity upon conversion to thrombin. The prothrombin sample used was from a heterozygote but contained exclusively a defective prothrombin molecule, since the patient was heterozygous for both dysprothrombinemia and hypoprothrombinemia. Amino acid sequence analysis of a peptide isolated from a lysyl endopeptidase digest of the abnormal thrombin indicated that Arg-418 (equivalent to Asn-101 in the chymotrypsin numbering system) had been replaced by Trp. This amino acid substitution can result from a single nucleotide change in the codon for Arg-418 (CGG-> TGG). The Arg-> Trp replacement found in the thrombin portion of prothrombin Tokushima appears to reduce its interaction with various substrates including fibrinogen and platelet receptors, and accounts for the recurrent bleeding episode observed in the propositus.
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Research Products
(19 results)
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[Publications] Kawabata, S., Miyata, T., Morita, T., Miyata, T., Iwanaga, S., and Igarashi, H.: "Tha Amino Acid Sequence of Procoagulant and Prothrombin-binding Domain Isolated from Staphylocoagulase." J. Biol. Chem.261(2). 527-531 (1986)
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[Publications] Kawauchi, S., Shirakami, A., Inomoto, T., Shigekiyo, T., Saito, S., Miyoshi, K., Morita, T., and Iwanaga, S.: "Prothrombin Tokushima: Characterization of Dysfunctional Thrombin Derived from a Variant of Human Prothrombin." Blood. February (1987)
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[Publications] Miyata, T., Morita, T., Inomoto, T., Kawauchi, S., Shirakami, A., and Iwanaga, S.: "Prothrombin Tokushima: A Replacement of Arginine-418 by Tryptophan that Impairs the Fibrinogen Clotting Activity of Derived Thrombin Tokushima." Biochemistry. Febrary. (1987)
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[Publications] Namamura, T., Horiuchi, T., M,orita, T., and Iwanaga, S.: "Purification and Characterization of Intracellular Clotting Factor, Factor B, from Horseshoe Crab (Tachypleus tridentatus) Hemocytes." J. Biochem.99. 847-857 (1986)
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[Publications] Aketagawa, J., Miyata, T., Ohtsubo, S., Nakamura, T., Morita, T., Hayashi, H., Miyata, T., Iwanaga, S., Takao, T., and Shimonishi, Y.: "Primary Structure of Limulus Anticoagulant, Anti-lipopolysaccharide Factor." J. Biol. Chem.261(16). 7357-7365 (1986)
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