Structural Aspects of the Factor X Activator RVV-X from Russell’s Viper Venom

  • Soichi TakedaEmail author


The venom of Russell’s viper Daboia russelli contains a potent blood coagulation factor X activator, RVV-X. Because of its high specificity, RVV-X is widely used in laboratories and as a diagnostic tool. RVV-X is a unique heterotrimeric metalloproteinase containing a mammalian a disintegrin and metalloproteinase (ADAM)-like heavy chain and two C-type lectin-like light chains, which are covalently held together by disulfide bonds. The crystal structure of RVV-X indicates that RVV-X adopts a “hook-spanner-wrench”–like structure, in which the metalloproteinase/disintegrin portion constitutes a mobile hook and the lectin-like domains, together with the remainder of the heavy chain, constitute a handle. The lectin-like domains form an intertwined dimer with high structural similarity to anticoagulant factor X-binding proteins. The RVV-X structure displayed a 6.5-nm separation between the catalytic zinc atom and a putative gamma carboxylglutamic acid (Gla) domain–binding exosite, implying molecular mechanism of factor X activation by RVV-X. The three-dimensional structure of RVV-X also provides a typical example of the molecular evolution of protein complexes, giving insight into the molecular basis of substrate recognition and proteolysis by adamalysin/reprolysin/ADAM family proteinases.


Light Chain Snake Venom Serine Proteinase Domain Epidermal Growth Factor Domain ADAMTS Protein 
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  1. Adler, M., Lazarus, R.A., Dennis, M.S., Wagner, G., 1991. Solution structure of kistrin, a potent platelet aggregation inhibitor and GP IIb-IIIa antagonist. Science 253, 445–448.PubMedCrossRefGoogle Scholar
  2. Akiyama, M., Takeda, S., Kokame, K., Takagi, J., Miyata, T., 2009. Crystal structures of the non-catalytic domains of ADAMTS13 reveal multiple discontinuous exosites for von Willebrand factor. Proc. Natl. Acad. Sci. U.S.A. 106, 19274–19279.PubMedCrossRefGoogle Scholar
  3. Apte, S.S., 2009. A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif (ADAMTS) superfamily-functions and mechanisms. J. Biol. Chem. 284, 31493–31497.PubMedCrossRefGoogle Scholar
  4. Atoda, H., Ishikawa, M., Mizuno, H., Morita, T., 1998. Coagulation factor X-binding protein from Deinagkistrodon acutus venom is a Gla domain-binding protein. Biochemistry 37, 17361–17370.PubMedCrossRefGoogle Scholar
  5. Banner, D.W., D’Arcy, A., Chene, C., Winkler, F.K., Guha, A., Konigsberg, W.H., Nemerson, Y., Kirchhofer, D., 1996. The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor. Nature 380, 41–46.PubMedCrossRefGoogle Scholar
  6. Batuwangala, T., Leduc, M., Gibbins, J.M., Bon, C., Jones, E.Y., 2004. Structure of the snake-venom toxin convulxin. Acta Crystallogr. D. Biol. Crystallogr. 60, 46–53.PubMedCrossRefGoogle Scholar
  7. Bjarnason, J.B., Fox, J.W., 1995. Snake venom metalloendopeptidases: reprolysins. Meth. Enzymol. 248, 345–368.PubMedCrossRefGoogle Scholar
  8. Black, R.A., Rauch, C.T., Kozlosky, C.J., Peschon, J.J., Slack, J.L., Wolfson, M.F., Castner, B.J., Stocking, K.L., Reddy, P., Srinivasan, S., Nelson, N., Boiani, N., Schooley, K.A., Gerhart, M., Davis, R., Fitzner, J.N., Johnson, R.S., Paxton, R.J., March, C.J., Cerretti, D.P., 1997. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature 385, 729–733.PubMedCrossRefGoogle Scholar
  9. Blobel, C.P., 2005. ADAMs: key components in EGFR signalling and development. Nat. Rev. Mol. Cell. Biol. 6, 32–43.PubMedCrossRefGoogle Scholar
  10. Blobel, C.P., Wolfsberg, T.G., Turck, C.W., Myles, D.G., Primakoff, P., White, J.M., 1992. A potential fusion peptide and an integrin ligand domain in a protein active in sperm-egg fusion. Nature 356, 248–252.PubMedCrossRefGoogle Scholar
  11. Bode, W., Gomis-Ruth, F.X., Stockler, W., 1993. Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the ‘metzincins’. FEBS Lett. 331, 134–140.PubMedCrossRefGoogle Scholar
  12. Calvete, J.J., Marcinkiewicz, C., Monleon, D., Esteve, V., Celda, B., Juarez, P., Sanz, L., 2005. Snake venom disintegrins: evolution of structure and function. Toxicon 45, 1063–1074.PubMedCrossRefGoogle Scholar
  13. Clemetson, K.J., Morita, T., Kini, R.M., 2009. Scientific and standardization committee communications: classification and nomenclature of snake venom C-type lectins and related proteins. J. Thromb. Haemost. 7, 360.PubMedCrossRefGoogle Scholar
  14. de Groot, R., Bardhan, A., Ramroop, N., Lane, D.A., Crawley, J.T., 2009. Essential role of the disintegrin-like domain in ADAMTS13 function. Blood 113, 5609–5616.PubMedGoogle Scholar
  15. Doley, R., Kini, R.M., 2009. Protein complexes in snake venom. Cell. Mol. Life Sci. 66, 2851–2871.PubMedCrossRefGoogle Scholar
  16. Duffy, M.J., Lynn, D.J., Lloyd, A.T., O’Shea, C.M., 2003. The ADAMs family of proteins: from basic studies to potential clinical applications. Thromb. Haemost. 89, 622–631.PubMedGoogle Scholar
  17. Edwards, D.R., Handsley, M.M., Pennington, C.J., 2009. The ADAM metalloproteinases. Mol. Aspects Med. 29, 258–289.CrossRefGoogle Scholar
  18. Evans, J.P., 2001. Fertilin beta and other ADAMs as integrin ligands: insights into cell adhesion and fertilization. Bioessays 23, 628–639.PubMedCrossRefGoogle Scholar
  19. Fox, J.W., Serrano, S.M., 2005. Structural considerations of the snake venom metalloproteinases, key members of the M12 reprolysin family of metalloproteinases. Toxicon 45, 969–985.PubMedCrossRefGoogle Scholar
  20. Fox, J.W., Serrano, S.M., 2008. Insights into and speculations about snake venom metalloproteinase (SVMP) synthesis, folding and disulfide bond formation and their contribution to venom complexity. FEBS J. 275, 3016–3030.PubMedCrossRefGoogle Scholar
  21. Freer, S.T., Kraut, J., Robertus, J.D., Wright, H.T., Xuong, N.H., 1970. Chymotrypsinogen: 2.5-Å crystal structure, comparison with α-chymotrypsin, and implications for zymogen activation. Biochemistry 9, 1997–2009.PubMedCrossRefGoogle Scholar
  22. Fujii, Y., Okuda, D., Fujimoto, Z., Horii, K., Morita, T., Mizuno, H., 2003. Crystal structure of trimestatin, a disintegrin containing a cell adhesion recognition motif RGD. J. Mol. Biol. 332, 1115–1122.PubMedCrossRefGoogle Scholar
  23. Fukuda, K., Mizuno, H., Atoda, H., Morita, T., 2000. Crystal structure of flavocetin-A, a platelet glycoprotein Ib-binding protein, reveals a novel cyclic tetramer of C-type lectin-like heterodimers. Biochemistry 39, 1915–1923.PubMedCrossRefGoogle Scholar
  24. Furie, B., Bouchard, B.A., Furie, B.C., 1999. Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid. Blood 93, 1798–1808.PubMedGoogle Scholar
  25. Gerhardt, S., Hassall, G., Hawtin, P., McCall, E., Flavell, L., Minshull, C., Hargreaves, D., Ting, A., Pauptit, R.A., Parker, A.E., Abbott, W.M., 2007. Crystal structures of human ADAMTS-1 reveal a conserved catalytic domain and a disintegrin-like domain with a fold homologous to cysteine-rich domains. J. Mol. Biol. 373, 891–902.PubMedCrossRefGoogle Scholar
  26. Gomis-Ruth, F.X., 2003. Structural aspects of the metzincin clan of metalloendopeptidases. Mol. Biotechnol. 24, 157–202.PubMedCrossRefGoogle Scholar
  27. Gomis-Ruth, F.X., Kress, L.F., Bode, W., 1993. First structure of a snake venom metalloproteinase: a prototype for matrix metalloproteinases/collagenases. EMBO J. 12, 4151–4157.PubMedGoogle Scholar
  28. Gomis-Ruth, F.X., Kress, L.F., Kellermann, J., Mayr, I., Lee, X., Huber, R., Bode, W., 1994. Refined 2.0 Å X-ray crystal structure of the snake venom zinc-endopeptidase adamalysin II. Primary and tertiary structure determination, refinement, molecular structure and comparison with astacin, collagenase and thermolysin. J. Mol. Biol. 239, 513–544.PubMedCrossRefGoogle Scholar
  29. Gowda, D.C., Jackson, C.M., Hensley, P., Davidson, E.A., 1994. Factor X-activating glycoprotein of Russell’s viper venom. Polypeptide composition and characterization of the carbohydrate moieties. J. Biol. Chem. 269, 10644–10650.PubMedGoogle Scholar
  30. Hite, L.A., Shannon, J.D., Bjarnason, J.B., Fox, J.W., 1992. Sequence of a cDNA clone encoding the zinc metalloproteinase hemorrhagic toxin e from Crotalus atrox: evidence for signal, zymogen, and disintegrin-like structures. Biochemistry 31, 6203–6211.PubMedCrossRefGoogle Scholar
  31. Hooley, E., Papagrigoriou, E., Navdaev, A., Pandey, A.V., Clemetson, J.M., Clemetson, K.J., Emsley, J., 2008. The crystal structure of the platelet activator aggretin reveals a novel (αβ)2 dimeric structure. Biochemistry 47, 7831–7837.PubMedCrossRefGoogle Scholar
  32. Huang, T.F., Holt, J.C., Lukasiewicz, H., Niewiarowski, S., 1987. Trigramin. A low molecular weight peptide inhibiting fibrinogen interaction with platelet receptors expressed on glycoprotein IIb-IIIa complex. J. Biol. Chem. 262, 16157–16163.PubMedGoogle Scholar
  33. Huber, R., Bode, W., 1978. Structural Basis of the activation and action of trypsin. Acc. Chem. Res. 11, 114–122.CrossRefGoogle Scholar
  34. Igarashi, T., Araki, S., Mori, H., Takeda, S., 2007. Crystal structures of catrocollastatin/VAP2B reveal a dynamic, modular architecture of ADAM/adamalysin/reprolysin family proteins. FEBS Lett. 581, 2416–2422.PubMedCrossRefGoogle Scholar
  35. Igarashi, T., Oishi, Y., Araki, S., Mori, H., Takeda, S., 2006. Crystallization and preliminary X-ray crystallographic analysis of two vascular apoptosis-inducing proteins (VAPs) from Crotalus atrox venom. Acta Crystallograph. F. Struct. Biol. Cryst. Commun. 62, 688–691.CrossRefGoogle Scholar
  36. Janes, P.W., Saha, N., Barton, W.A., Kolev, M.V., Wimmer-Kleikamp, S.H., Nievergall, E., Blobel, C.P., Himanen, J.P., Lackmann, M., Nikolov, D.B., 2005. Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 123, 291–304.PubMedCrossRefGoogle Scholar
  37. Kamata, K., Kawamoto, H., Honma, T., Iwama, T., Kim, S.H., 1998. Structural basis for chemical inhibition of human blood coagulation factor Xa. Proc. Natl. Acad. Sci. U.S.A. 95, 6630–6635.PubMedCrossRefGoogle Scholar
  38. Kisiel, W., Hermodson, M.A., Davie, E.W., 1976. Factor X activating enzyme from Russell’s viper venom: isolation and characterization. Biochemistry 15, 4901–4906.PubMedCrossRefGoogle Scholar
  39. Kuno, K., Kanada, N., Nakashima, E., Fujiki, F., Ichimura, F., Matsushima, K., 1997. Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated gene. J. Biol. Chem. 272, 556–562.PubMedCrossRefGoogle Scholar
  40. Lindhout, M.J., Kop-Klaassen, B.H., Hemker, H.C., 1978. Activation of decarboxyfactor X by a protein from Russell’s viper venom. Purification and partial characterization of activated decarboxyfactor X. Biochim. Biophys. Acta, 533, 327–341.PubMedCrossRefGoogle Scholar
  41. Liu, H., Shim, A.H., He, X., 2009. Structural characterization of the ectodomain of a disintegrin and metalloproteinase-22 (ADAM22), a neural adhesion receptor instead of metalloproteinase: insights on ADAM function. J. Biol. Chem. 284, 29077–29086.PubMedCrossRefGoogle Scholar
  42. Mann, K.G., Nesheim, M.E., Church, W.R., Haley, P., Krishnaswamy, S., 1990. Surface-dependent reactions of the vitamin K-dependent enzyme complexes. Blood 76, 1–16.PubMedGoogle Scholar
  43. Mizuno, H., Fujimoto, Z., Atoda, H., Morita, T., 2001. Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X. Proc. Natl. Acad. Sci. U.S.A. 98, 7230–7234.PubMedCrossRefGoogle Scholar
  44. Mizuno, H., Fujimoto, Z., Koizumi, M., Kano, H., Atoda, H., Morita, T., 1997. Structure of coagulation factors IX/X-binding protein, a heterodimer of C-type lectin domains. Nat. Struct. Biol. 4, 438–441.PubMedCrossRefGoogle Scholar
  45. Mochizuki, S., Okada, Y., 2007. ADAMs in cancer cell proliferation and progression. Cancer Sci. 98, 621–628.PubMedCrossRefGoogle Scholar
  46. Morita, T., 1998. Proteases which Activate Factor X. Alaken, Colorado.Google Scholar
  47. Morita, T., 2005. Structures and functions of snake venom CLPs (C-type lectin-like proteins) with anticoagulant-, procoagulant-, and platelet-modulating activities. Toxicon 45, 1099–1114.PubMedCrossRefGoogle Scholar
  48. Morita, T., Jackson, C.M., 1986. Preparation and properties of derivatives of bovine factor X and factor Xa from which the gamma-carboxyglutamic acid containing domain has been removed. J. Biol. Chem. 261, 4015–4023.PubMedGoogle Scholar
  49. Moss, M.L., Bartsch, J.W., 2004. Therapeutic benefits from targeting of ADAM family members. Biochemistry 43, 7227–7235.PubMedCrossRefGoogle Scholar
  50. Moss, M.L., Jin, S.L., Milla, M.E., Bickett, D.M., Burkhart, W., Carter, H.L., Chen, W.J., Clay, W.C., Didsbury, J.R., Hassler, D., Hoffman, C.R., Kost, T.A., Lambert, M.H., Leesnitzer, M.A., McCauley, P., McGeehan, G., Mitchell, J., Moyer, M., Pahel, G., Rocque, W., Overton, L.K., Schoenen, F., Seaton, T., Su, J.L., Warner, J., Willard, D., Becherer, J.D., 1997. Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature 385, 733–736.PubMedCrossRefGoogle Scholar
  51. Mosyak, L., Georgiadis, K., Shane, T., Svenson, K., Hebert, T., McDonagh, T., Mackie, S., Olland, S., Lin, L., Zhong, X., Kriz, R., Reifenberg, E.L., Collins-Racie, L.A., Corcoran, C., Freeman, B., Zollner, R., Marvell, T., Vera, M., Sum, P.E., Lavallie, E.R., Stahl, M., Somers, W., 2008. Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5. Protein Sci. 17, 16–21.PubMedCrossRefGoogle Scholar
  52. Muniz, J.R., Ambrosio, A.L., Selistre-de-Araujo, H.S., Cominetti, M.R., Moura-da-Silva, A.M., Oliva, G., Garratt, R.C., Souza, D.H., 2008. The three-dimensional structure of bothropasin, the main hemorrhagic factor from Bothrops jararaca venom: insights for a new classification of snake venom metalloprotease subgroups. Toxicon 52, 807–816.PubMedCrossRefGoogle Scholar
  53. Murakami, M.T., Zela, S.P., Gava, L.M., Michelan-Duarte, S., Cintra, A.C., Arni, R.K., 2003. Crystal structure of the platelet activator convulxin, a disulfide-linked α4β4 cyclic tetramer from the venom of Crotalus durissus terrificus. Biochem. Biophys. Res. Commun. 310, 478–482.PubMedCrossRefGoogle Scholar
  54. Murphy, G., 2008. The ADAMs: signalling scissors in the tumour microenvironment. Nat. Rev. Cancer 8, 929–941.PubMedCrossRefGoogle Scholar
  55. Okuda, D., Koike, H., Morita, T., 2002. A new gene structure of the disintegrin family: a subunit of dimeric disintegrin has a short coding region. Biochemistry 41, 14248–14254.PubMedCrossRefGoogle Scholar
  56. Padmanabhan, K., Padmanabhan, K.P., Tulinsky, A., Park, C.H., Bode, W., Huber, R., Blankenship, D.T., Cardin, A.D., Kisiel, W., 1993. Structure of human des(1–45) factor Xa at 2.2 Å resolution. J. Mol. Biol. 232, 947–966.PubMedCrossRefGoogle Scholar
  57. Papagrigoriou, E., McEwan, P.A., Walsh, P.N., Emsley, J., 2006. Crystal structure of the factor XI zymogen reveals a pathway for transactivation. Nat. Struct. Mol. Biol. 13, 557–558.PubMedCrossRefGoogle Scholar
  58. Peschon, J.J., Slack, J.L., Reddy, P., Stocking, K.L., Sunnarborg, S.W., Lee, D.C., Russell, W.E., Castner, B.J., Johnson, R.S., Fitzner, J.N., Boyce, R.W., Nelson, N., Kozlosky, C.J., Wolfson, M.F., Rauch, C.T., Cerretti, D.P., Paxton, R.J., March, C.J., Black, R.A., 1998. An essential role for ectodomain shedding in mammalian development. Science 282, 1281–1284.PubMedCrossRefGoogle Scholar
  59. Porter, S., Clark, I.M., Kevorkian, L., Edwards, D.R., 2005. The ADAMTS metalloproteinases. Biochem. J. 386, 15–27.PubMedCrossRefGoogle Scholar
  60. Saudek, V., Atkinson, R.A., Pelton, J.T., 1991. Three-dimensional structure of echistatin, the smallest active RGD protein. Biochemistry 30, 7369–7372.PubMedCrossRefGoogle Scholar
  61. Seals, D.F., Courtneidge, S.A., 2003. The ADAMs family of metalloproteases: multidomain proteins with multiple functions. Genes Dev. 17, 7–30.PubMedCrossRefGoogle Scholar
  62. Senn, H., Klaus, W., 1993. The nuclear magnetic resonance solution structure of flavoridin, an antagonist of the platelet GP IIb-IIIa receptor. J. Mol. Biol. 232, 907–925.PubMedCrossRefGoogle Scholar
  63. Siigur, E., Aaspollu, A., Trummal, K., Tonismagi, K., Tammiste, I., Kalkkinen, N., Siigur, J., 2004. Factor X activator from Vipera lebetina venom is synthesized from different genes. Biochim. Biophys. Acta 1702, 41–51.PubMedCrossRefGoogle Scholar
  64. Skogen, W.F., Bushong, D.S., Johnson, A.E., Cox, A.C., 1983. The role of the Gla domain in the activation of bovine coagulation factor X by the snake venom protein XCP. Biochem. Biophys. Res. Commun. 111, 14–20.PubMedCrossRefGoogle Scholar
  65. Takeda, S., 2008. VAP1: snake venom homolog of mammalian ADAMs, in: Messerschmidt, A. (Ed.), Handbook of Metalloproteins. John Wiley & Sons, Inc., City, pp. 1–15.Google Scholar
  66. Takeda, S., 2009. Three-dimensional domain architecture of the ADAM family proteinases. Semin. Cell Dev. Biol. 20, 146–152.PubMedCrossRefGoogle Scholar
  67. Takeda, S., Igarashi, T., Mori, H., 2007. Crystal structure of RVV-X: an example of evolutionary gain of specificity by ADAM proteinases. FEBS Lett. 581, 5859–5864.PubMedCrossRefGoogle Scholar
  68. Takeda, S., Igarashi, T., Mori, H., Araki, S., 2006. Crystal structures of VAP1 reveal ADAMs’ MDC domain architecture and its unique C-shaped scaffold. EMBO J. 25, 2388–2396.PubMedCrossRefGoogle Scholar
  69. Takeya, H., Nishida, S., Miyata, T., Kawada, S., Saisaka, Y., Morita, T., Iwanaga, S., 1992. Coagulation factor X activating enzyme from Russell’s viper venom (RVV-X). A novel metalloproteinase with disintegrin (platelet aggregation inhibitor)-like and C-type lectin-like domains. J. Biol. Chem. 267, 14109–14117.PubMedGoogle Scholar
  70. Takeya, H., Nishida, S., Nishino, N., Makinose, Y., Omori-Satoh, T., Nikai, T., Sugihara, H., Iwanaga, S., 1993. Primary structures of platelet aggregation inhibitors (disintegrins) autoproteolytically released from snake venom hemorrhagic metalloproteinases and new fluorogenic peptide substrates for these enzymes. J. Biochem. (Tokyo) 113, 473–483.Google Scholar
  71. Tans, G., Rosing, J., 2001. Snake venom activators of factor X: an overview. Haemostasis 31, 225–233.PubMedGoogle Scholar
  72. Wang, D., Bode, W., Huber, R., 1985. Bovine chymotrypsinogen A X-ray crystal structure analysis and refinement of a new crystal form at 1.8 Å resolution. J. Mol. Biol. 185, 595–624.PubMedCrossRefGoogle Scholar
  73. Wang, S.X., Hur, E., Sousa, C.A., Brinen, L., Slivka, E.J., Fletterick, R.J., 2003. The extended interactions and Gla domain of blood coagulation factor Xa. Biochemistry 42, 7959–7966.PubMedCrossRefGoogle Scholar
  74. Weis, W.I., Kahn, R., Fourme, R., Drickamer, K., Hendrickson, W.A., 1991. Structure of the calcium-dependent lectin domain from a rat mannose-binding protein determined by MAD phasing. Science 254, 1608–1615.PubMedCrossRefGoogle Scholar
  75. White, J.M., 2003. ADAMs: modulators of cell-cell and cell-matrix interactions. Curr. Opin. Cell. Biol. 15, 598–606.PubMedCrossRefGoogle Scholar
  76. White, J.M., Bidges, L., DeSimone, D.W., Tomczuk, M., Wolfsberg, T.G. 2005. Introduction to the ADAM family, in: Hooper, N.M., Lendeckel, U. (Eds.), The ADAM Family of Proteinases (vol. 4). Springer, Dordrecht, The Netherlands, pp. 1–29.CrossRefGoogle Scholar
  77. Yagami-Hiromasa, T., Sato, T., Kurisaki, T., Kamijo, K., Nabeshima, Y., Fujisawa-Sehara, A., 1995. A metalloprotease-disintegrin participating in myoblast fusion. Nature 377, 652–656.PubMedCrossRefGoogle Scholar
  78. Yamada, D., Sekiya, F., Morita, T., 1996. Isolation and characterization of carinactivase, a novel prothrombin activator in Echis carinatus venom with a unique catalytic mechanism. J. Biol. Chem. 271, 5200–5207.PubMedCrossRefGoogle Scholar
  79. Zelensky, A.N., Gready, J.E., 2005. The C-type lectin-like domain superfamily. FEBS J. 272, 6179–6217.PubMedCrossRefGoogle Scholar
  80. Zhu, Z., Gao, Y., Yu, Y., Zhang, X., Zang, J., Teng, M., Niu, L., 2009. Structural basis of the autolysis of AaHIV suggests a novel target recognizing model for ADAM/reprolysin family proteins. Biochem. Biophys. Res. Commun. 386, 159–164.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.National Cerebral and Cardiovascular Center Research InstituteSuitaJapan

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