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A Computer Modeling Study of the Interaction Between Tissue Factor Pathway Inhibitor and Blood Coagulation Factor Xa

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Abstract

Activation of blood coagulation factor X to factor Xa (FXa) is inhibited by tissue factor pathway inhibitor (TFPI). The second Kunitz-type inhibitory domain (K2) of TFPI binds a catalytic domain of FXa, whereas the first domain (K1) does not. We analyzed computer models of complexes of FXa with K1 or K2, which were made using a crystal structure of FXa. Favorable hydrophobic interaction was observed in the complex of FXa with K2. Furthermore, we constructed a tertiary structure of FXa using CHIMERA to assess the accuracy of a homology modeling method. The isolated model structure of FXa agreed well with the crystal structure, but analyses of complexes of this structure with K1 or K2 revealed that the models of complexes could not provide clear evidence of greater binding ability to K2 because of the positional difference of a few side chains interacting with the inhibitor.

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REFERENCES

  • Bernstein, F. C., Koetzle, T. F., Williams, G. J. B., Meyer, Jr., E. F., Brice, M. D., Rodgers, J. R., Kennard, O., Shimanouchi, T., and Tasumi, M. (1977). J. Mol. Biol. 112, 535–542.

    Article  CAS  PubMed  Google Scholar 

  • Blevins, R. A., and Tulinsky, A. (1985). J. Biol. Chem. 260, 4264–4275.

    Article  CAS  PubMed  Google Scholar 

  • Blundell, T., Carney, D., Gardner, S., Hayes, F., Howlin, B., Hubbard, T., Overington, J., Singh, D. A., Sibanda, B. L., and Sutcliffe, M. (1988). Eur. J. Biochem. 172, 513–520.

    Article  CAS  PubMed  Google Scholar 

  • Bode, W., Chen, Z., Bartels, K., Kutzbach, C., Schmidt-Kastner, G., and Bartunik, H. (1983). J. Mol. Biol. 164, 237–282.

    Article  CAS  PubMed  Google Scholar 

  • Bode, W., Walter, J., Huber, R., Wenzel, H. R., and Tschesche, H. (1984). Eur. J. Biochem. 144, 185–190.

    Article  CAS  PubMed  Google Scholar 

  • Bode, W., Mayr, I., Baumann, U., Huber, R., Stone, S. R., and Hofsteenge, J. (1989). EMBO J. 8, 3467–3475.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Broze, Jr., G. J. (1995). Annu. Rev. Med. 46, 103–112.

    Article  CAS  PubMed  Google Scholar 

  • Fujinaga, M., and James, M. N. G. (1987). J. Mol. Biol. 195, 373–396.

    Article  CAS  PubMed  Google Scholar 

  • Greer, J. (1990). Proteins 7, 317–334.

    Article  CAS  PubMed  Google Scholar 

  • Johnson, M. S., Srinivasan, N., Sowdhamini, R., and Blundell, T. L. (1994). Crit. Rev. Biochem. Mol. Biol. 29, 1–68.

    Article  CAS  PubMed  Google Scholar 

  • Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W., and Klein, M. L. (1983). J. Chem. Phys. 79, 926–935.

    Article  CAS  Google Scholar 

  • Kajihara, A., Komooka, H., Kamiya, K., and Umeyama, H. (1993). Protein Eng. 6, 615–620.

    Article  CAS  PubMed  Google Scholar 

  • Katakura, S., Nagahara, T., Hara, T., Kunitada, S., and Iwamoto, M. (1995). Eur. J. Med. Chem. 30, 387–394.

    Article  CAS  Google Scholar 

  • Marquart, M., Walter, J., Deisenhofer, J., Bode, W., and Huber, R. (1983). Acta Crystallogr. B 39, 480–490.

    Article  Google Scholar 

  • Matsusue, T., Yoneda, T., Komooka, H., Kamiya, K., Shinomiya, K., and Umeyama, H. (n.d.). To be published.

  • Meyer, E., Cole, G., Radhakrishnan, R., and Epp, O. (1988). Acta Crystallogr. B 44, 26–38.

    Article  PubMed  Google Scholar 

  • Miyata, T., Kuze, K., Matsusue, T., Komooka, H., Kamiya, K., Umeyama, H., Matsui, A., Kato, H., and Yoshioka, A. (1994). Brit. J. Haematol. 88, 156–165.

    Article  CAS  Google Scholar 

  • Nii, A., Morishita, H., Yamakawa, T., Matsusue, T., Hirose, J., Miura, T., Isaji, M., Horisawa, Y., Sugihara, K., Kanamori, T., and Umeyama, H. (1994). J. Biochem. 115, 1107–1112.

    Article  CAS  PubMed  Google Scholar 

  • Padmanabhan, K., Padmanabhan, K. P., Tulinsky, A., Park, C. H., Bode, W., Huber, R., Blankenship, D. T., Cardin, A. D., and Kisiel, W. (1993). J. Mol. Biol. 232, 947–966.

    Article  CAS  PubMed  Google Scholar 

  • Remington, S. J., Woodbury, R. G., Reynolds, R. A., Matthews, B. W., and Neurath, H. (1988). Biochemistry 27, 8097–8105.

    Article  CAS  PubMed  Google Scholar 

  • Ripka, W., Brunck, T., Stanssens, P., LaRoche, Y., Lauwereys, M., Lambeir, A.-M., Lasters, I., DeMaeyer, M., Vlasuk, G., Levy, O., Miller, T., Webb, T., Tamura, S., and Pearson, D. (1995). Eur. J. Med. Chem. 30, 87s–100s.

    Article  CAS  Google Scholar 

  • Stubbs, M. T., Huber, R., and Bode, W. (1995). FEBS Lett. 375, 103–107.

    Article  CAS  PubMed  Google Scholar 

  • Weiner, S. J., Kollman, P. A., Case, D. A., Singh, U. C., Ghio, C., Alagona, G., Profeta, Jr., S., and Weiner, P. (1984). J. Am. Chem. Soc. 106, 765–784.

    Article  CAS  Google Scholar 

  • Yoneda, S., and Umeyama, H. (1992). J. Chem. Phys. 97, 6730–6736.

    Article  CAS  Google Scholar 

  • Zheng, Y.-Z., Sakata, T., Matsusue, T., Umeyama, H., Kato, H., and Miyata, T. (1994). Blood Coagul. Fibrin. 5, 687–696.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108, Japan

    Teruyo Yoneda, Hitoshi Komooka & Hideaki Umeyama

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  1. Teruyo Yoneda
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  2. Hitoshi Komooka
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  3. Hideaki Umeyama
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Yoneda, T., Komooka, H. & Umeyama, H. A Computer Modeling Study of the Interaction Between Tissue Factor Pathway Inhibitor and Blood Coagulation Factor Xa. J Protein Chem 16, 597–605 (1997). https://doi.org/10.1023/A:1026318823516

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  • DOI: https://doi.org/10.1023/A:1026318823516

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