| Co-Investigator(Kenkyū-buntansha) |
HAMAKO Jiharu Fujita Health University, Coll., Associate Professor, 短期大学・医療情報技術科, 助教授 (80180933)
TITANI Koiti Fujita Health University, Inst. Comprehensive Med. Sci., Research Associate, 総合医科学研究所, 研究員 (60179942)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
We have screened lectins that can recognize the difference in the carbohydrate structures on von Willebrand factor (VWF) from normal individuals with each ABO blood group and patients with type 1 von Willebrand disease (VWD). Furthermore, we have studied the structure and function of snake venom proteins affecting human hemostasis by interacting with VWF and platelet.
1) Among blood group-reconizing lectins examined, HPA and UEA-I were useful for detection and fractionation of blood group A and O(H) sugar chains on VWF, respectively (BBA, 1525: 50-57, 2001). We have found that the sialic acid-recognizing lectins (SSA and SNA) and the H structure-recognizing lectins (TJA-I and UEA-I) preferentially bound to VWF from group O and type 1 VWD plasmas, suggesting that these VWFs contain terminal sialic acid residues and the H structure in a higher amount.
2) We have determined the amino acid sequence of kaouthiagin which specifically cleaves VWF, and found that its Cys-rich domain has the functional disintegrin-like activity (Biochemistry 40: 4503-4511, 2001). We have determined the crystal structure of bitiscetin which modulates VWF to induce platelet aggregation, and found that it has a central conecave structure rich in negatively charged residues, implying that it might be the VWF-binding site (Biochemistry 40: 13592-13597, 2001).
3) We have found that the deficiency of physiological VWF-cleaving metalloproteinase in plasma causes the presence of ultra-high molecular mass multimers of VWF subunits resulting in the Upshaw-Schulman syndrome (USS), the congenital thrombotic thrombocytopenic purpura (TTP). (Int. J. Hematol, 74: 101-108, 2001, Int. J. Hematol., 75: 25-34, 2002).
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