Inhibition of the Serine Proteases of the Complement System

  • Péter GálEmail author
  • József Dobó
  • László Beinrohr
  • Gábor Pál
  • Péter Závodszky
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 735)


Proteases play important roles in human physiology and pathology. The complement ­system is a proteolytic cascade, where serine proteases activate each other by limited proteolysis in a strictly ordered manner. Serine proteases are essential in both the initiation and the amplification of the cascade. Since uncontrolled complement activation contributes to the development of serious disease conditions, inhibition of the complement serine proteases could be an attractive therapeutic approach. In this chapter, we give a brief overview of the major types of natural serine protease inhibitors and their role in controlling the complement cascade. A special emphasis is laid on C1-inhibitor, a natural complement protease inhibitor, which is approved for clinical use in hereditary angioedema (HAE). We also examine the potential of developing artificial complement protease inhibitors. Synthetic small-molecule drugs can be very efficient serine protease inhibitors, but they usually lack sufficient specificity. A promising approach to yield more specific compounds is the alteration of natural protease inhibitors through engineering or directed evolution resulting in new variants with fine-tuned specificity and enhanced affinity.


Serine Protease Hereditary Angioedema Lectin Pathway Plasma Kallikrein Reactive Center Loop 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by the Ányos Jedlik grant NKFP_07_1-MASPOK07, the Hungarian Scientific Research Fund (OTKA) grant NK77978, NK100834, K68408, NK81950 and NK100769 and the NDA grant KMOP-1.1.2-07/1-2008-0003 and the National Development Agency Grant KMOP-1.1.2-07/1-2008-0003 as well as by the European Union and the European Social Fund (TÁMOP) 4.2.1./B-09/KMR-2010-0003 grant.


  1. Ambrus G, Gál P, Kojima M, Szilágyi K, Balczer J, Antal J, Gráf L, Laich A, Moffatt BE, Schwaeble W, Sim RB, Závodszky P (2003) Natural substrates and inhibitors of mannan-binding lectin-associated serine protease-1 and -2: a study on recombinant catalytic fragments. J Immunol 170:1374–1382CrossRefGoogle Scholar
  2. Beinrohr L, Harmat V, Dobó J, Lőrincz Z, Gál P, Závodszky P (2007) C1 inhibitor serpin domain structure reveals the likely mechanism of heparin potentiation and conformational disease. J Biol Chem 282:21100–21109CrossRefGoogle Scholar
  3. Beinrohr L, Dobó J, Závodszky P, Gál P (2008) C1, MBL-MASPs and C1-inhibitor: novel approaches for targeting complement-mediated inflammation. Trends Mol Med 14:511–521CrossRefGoogle Scholar
  4. Bode W, Huber R (1992) Natural protein proteinase inhibitors and their interaction with proteinases. Eur J Biochem 204:433–451CrossRefGoogle Scholar
  5. Broze GJ Jr, Warren LA, Novotny WF, Higuchi DA, Girard JJ, Miletich JP (1988) The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action. Blood 71:335–343PubMedGoogle Scholar
  6. Buerke M, Murohara T, Lefer AM (1995) Cardioprotective effects of a C1 esterase inhibitor in myocardial ischemia and reperfusion. Circulation 91:393–402CrossRefGoogle Scholar
  7. Buerke M, Schwertz H, Seitz W, Meyer J, Darius H (2001) Novel small molecule inhibitor of C1s exerts cardioprotective effects in ischemia-reperfusion injury in rabbits. J Immunol 167:5375–5380CrossRefGoogle Scholar
  8. Cai S, Davis AE III (2003) Complement regulatory protein C1 inhibitor binds to selectins and interferes with endothelial-leukocyte adhesion. J Immunol 171:4786–4791CrossRefGoogle Scholar
  9. Chen CB, Wallis R (2004) Two mechanisms for mannose-binding protein modulation of the activity of its associated serine proteases. J Biol Chem 279:26058–26065CrossRefGoogle Scholar
  10. Dahl MR, Thiel S, Matsushita M, Fujita T, Willis AC, Christensen T, Vorup-Jensen T, Jensenius JC (2001) MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway. Immunity 15:127–135CrossRefGoogle Scholar
  11. Davis AE III, Mejia P, Lu F (2008) Biological activities of C1 inhibitor. Mol Immunol 45:4057–4063CrossRefPubMedPubMedCentralGoogle Scholar
  12. Davis AE III, Lu F, Mejia P (2010) C1 inhibitor, a multi-functional serine protease inhibitor. Thromb Haemost 104:886–893CrossRefGoogle Scholar
  13. Degn SE, Hansen AG, Steffensen R, Jacobsen C, Jensenius JC, Thiel S (2009) MAp44, a human protein associated with pattern recognition molecules of the complement system and regulating the lectin pathway of complement activation. J Immunol 183:7371–7378CrossRefGoogle Scholar
  14. Dobó J, Harmat V, Beinrohr L, Sebestyén E, Závodszky P, Gál P (2009) MASP-1, a promiscuous complement protease: structure of its catalytic region reveals the basis of its broad specificity. J Immunol 183:1207–1214CrossRefGoogle Scholar
  15. Dommet RM, Klein N, Turner MW (2006) Mannose-binding lectin in innate immunity, past, present and future. Tissue Antigens 68:193–209CrossRefGoogle Scholar
  16. Endo Y, Matsushita M, Fujita T (2011) The role of ficolins in the lectin pathway of innate immunity. Int J Biochem Cell Biol 43:705–712CrossRefGoogle Scholar
  17. Epstein TG, Bernstein JA (2008) Current and emerging management options for hereditary angioedema. Drugs 68:2561–2573CrossRefGoogle Scholar
  18. Farady CJ, Sun J, Darragh MR, Miller SM, Craik CS (2007) The mechanism of inhibition of antibody-based inhibitors of membrane-type serine protease 1 (MT-SP1). J Mol Biol 369:1041–1051CrossRefPubMedPubMedCentralGoogle Scholar
  19. Fattouch K, Bianco G, Speziale G, Sampognaro R, Lavalle C, Guccione F, Dioguardi P, Ruvolo G (2007) Beneficial effects of C1 esterase inhibitor in ST-elevation myocardial infarction in patients who underwent surgical reperfusion: a randomised double-blind study. Eur J Cardiothorac Surg 32:326–332CrossRefPubMedPubMedCentralGoogle Scholar
  20. Fujii S, Hitomi Y (1981) New synthetic inhibitors of C1r, C1 esterase, thrombin, plasmin, kallikrein and trypsin. Biochim Biophys Acta 661:342–345CrossRefPubMedPubMedCentralGoogle Scholar
  21. Gál P, Harmat V, Kocsis A, Bián T, Barna L, Ambrus G, Végh B, Balczer J, Sim RB, Náray-Szabó G, Závodszky P (2005) A true autoactivating enzyme. Structural insight into mannose-binding lectin-associated serine protease-2 activations. J Biol Chem 280:33435–33444CrossRefPubMedPubMedCentralGoogle Scholar
  22. Gál P, Dobó J, Závodszky P, Sim RBM (2009) Early complement proteases: C1r, C1s and MASPs. A structural insight into activation and functions. Mol Immunol 46:2745–2752CrossRefPubMedPubMedCentralGoogle Scholar
  23. Ganesan R, Eigenbrot C, Wu Y, Liang WC, Shia S, Lipari MT, Kirchhofer D (2009) Unraveling the allosteric mechanism of serine protease inhibition by an antibody. Structure 17:1614–1624CrossRefGoogle Scholar
  24. Gesuete R, Storini C, Fantin A, Stravalaci M, Zanier ER, Orsini F, Vietsch H, Mannesse ML, Ziere B, Gobbi M, De Simoni MG (2009) Recombinant C1 inhibitor in brain ischemic injury. Ann Neurol 66:332–342CrossRefGoogle Scholar
  25. Gettins PG (2002) Serpin structure, mechanism, and function. Chem Rev 102:4751–4804CrossRefGoogle Scholar
  26. Gettins PGW, Olson ST (2009) Exosite determinants of serpin specificity. J Biol Chem 284:20441–20445CrossRefPubMedPubMedCentralGoogle Scholar
  27. Grütter MG, Priestle JP, Rahuel J, Grossenbacher H, Bode W, Hofsteenge J, Stone SR (1990) Crystal structure of the thrombin-hirudin complex: a novel mode of serine protease inhibition. EMBO J 9:2361–2365CrossRefPubMedPubMedCentralGoogle Scholar
  28. Halili MA, Ruiz-Gómez G, Le GT, Abbenante G, Fairlie DP (2009) Complement component C2, inhibiting a latent serine protease in the classical pathway of complement activation. Biochemistry 48:8466–8472CrossRefGoogle Scholar
  29. Hansen S, Selman L, Palaniyar N, Ziegler K, Brandt J, Kliem A, Jonasson M, Skjoedt MO, Nielsen O, Hartshorn K, Jørgensen TJ, Skjødt K, Holmskov U (2010) Collectin 11 (CL-11, CL-K1) is a MASP-1/3-associated plasma collectin with microbial-binding activity. J Immunol 185:6096–6104CrossRefGoogle Scholar
  30. Hedstrom L (2002) Serine protease mechanism and specificity. Chem Rev 102:4501–4524CrossRefGoogle Scholar
  31. Héja D, Harmat V, Fodor K, Wilmanns M, Dobó J, Kékesi KA, Závodszky P, Gál P, Pál G (2012a) Monospecific inhibitors show that both mannan-binding lectin-associated serine protease (MASP)-1 and -2 are essential for lectin pathway activation and reveal structural plasticity of MASP-2. J Biol Chem 287:20290–20300CrossRefGoogle Scholar
  32. Héja D, Kocsis A, Dobó J, Szilágyi K, Szász R, Závodszky P, Pál G, Gál P (2012b) Revised mechanism of complement lectin-pathway activation revealing the role of serine protease MASP-1 as the exclusive activator of MASP-2. Proc Natl Acad Sci USA 10.1073/pnas.1202588109CrossRefGoogle Scholar
  33. Holers VM (2008) The spectrum of complement alternative pathway-mediated diseases. Immunol Rev 233:300–316CrossRefGoogle Scholar
  34. Iwaki D, Kanno K, Takahashi M, Endo Y, Matsushita M, Fujita T (2011) The role of mannose-binding lectin-associated serine protease-3 in activation of the alternative complement pathway. J Immunol 187:3751–3758CrossRefGoogle Scholar
  35. Jackson RM, Russel RB (2000) The serine protease inhibitor canonical loop conformation: examples found in extracellular hydrolases, toxins, cytokines and viral proteins. J Mol Biol 296:325–334CrossRefGoogle Scholar
  36. Jiang H, Wagner E, Zhang H, Frank MM (2001) Complement 1 inhibitor is a regulator of the alternative complement pathway. J Exp Med 194:1609–1916CrossRefPubMedPubMedCentralGoogle Scholar
  37. Kaplan AP, Ghebrehiwet B (2010) The plasma bradykinin-forming pathways and its interrelationships with complement. Mol Immunol 47:2161–2169CrossRefGoogle Scholar
  38. Kemper C, Hourcade DE (2008) Properdin: New roles in pattern recognition and target clearance. Mol Immunol 45: 4048–4056CrossRefGoogle Scholar
  39. Kocsis A, Kékesi KA, Szász R, Végh BM, Balczer J, Dobó J, Závodszky P, Gál P, Pál G (2010) Selective inhibition of the lectin pathway of complement with phage display selected peptides against mannose-binding lectin-associated serine protease (MASP)-1 and -2: significant contribution of MASP-1 to lectin pathway activation. J Immunol 185:4169–4178CrossRefGoogle Scholar
  40. Krem MM, Di Cera E (2002) Evolution of enzyme cascades from embryonic development to blood coagulation. Trends Biochem Sci 27:67–74CrossRefGoogle Scholar
  41. Krowarsch D, Cierpicki T, Jelen F, Otlewski J (2003) Canonical protein inhibitors of serine proteases. Cell Mol Life Sci 60:2427–2444CrossRefGoogle Scholar
  42. Laskowski M Jr (1986) Protein inhibitors of serine proteinases – mechanism and classification. Adv Exp Med Biol 199:1–17CrossRefGoogle Scholar
  43. Lathem WW, Bergsbaken T, Welch RA (2004) Potentiation of C1 esterase inhibitor by StcE, a metalloprotease secreted by Escherichia coli O157:H7. J Exp Med 199:1077–1087CrossRefPubMedPubMedCentralGoogle Scholar
  44. López-Otín C, Bond JS (2008) Proteases: multifunctional enzymes in life and disease. J Biol Chem 283:30433–30437CrossRefPubMedPubMedCentralGoogle Scholar
  45. Lunn M, Banta E (2011) Ecallantide for the treatment of hereditary angioedema in adults. Clin Med Insights Cardiol 5:49–54CrossRefPubMedPubMedCentralGoogle Scholar
  46. Markland W, Ley AC, Ladner RC (1996) Iterative optimization of high-affinity protease inhibitors using phage display. 2. Plasma kallikrein and thrombin. Biochemistry 35:8058–8067CrossRefGoogle Scholar
  47. Marrero A, Duquerroy S, Trapani S, Goulas T, Guevara T, Andersen GR, Navaza J, Sottrup-Jensen L, Gomis-Rüth FX (2012) The crystal structure of human α(2)-macroglobulin reveals a unique molecular cage. Angew Chem Int Ed Engl 10.1002/anie.201108015CrossRefGoogle Scholar
  48. Moller-Kristensen M, Thiel S, Sjoholm A, Matsushita M, Jensenius JC (2007) Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway. Int Immunol 19:141–149CrossRefGoogle Scholar
  49. Nayak A, Pedenekar L, Reid KB, Kishore U (2011) Complement and non-complement activating functions of C1q: a prototypical innate immune molecule. Innate Immun. doi: 10.1177/1753425910396252
  50. Neurath H (1984) Evolution of proteolytic enzymes. Science 224:350–357CrossRefGoogle Scholar
  51. Nilsson SC, Sim RB, Lea SM, Fremeaux-Bacchi V, Blom AM (2011) Complement factor I in health and disease. Mol Immunol 48:1611–1620CrossRefGoogle Scholar
  52. Page MJ, Di Cera E (2008) Serine peptidases: classification, structure and function. Cell Mol Life Sci 65:1220–1236CrossRefGoogle Scholar
  53. Pike RN, Bottomley SP, Irving JA, Bird PI, Whisstock JC (2002) Serpins: finely balanced conformational traps. IUBMB Life 54:1–7CrossRefGoogle Scholar
  54. Pike RN, Buckle AM, le Bonniec BF, Church FC (2005) Control of the coagulation system by serpins. Getting by with a little help from glycosaminoglycans. FEBS J 272:4842–4851CrossRefGoogle Scholar
  55. Puente XS, Sanchez LM, Gutierrez-Fernandez A, Velasco G, Lopez-Otin C (2005) A genomic view of the complexity of mammalian proteolytic systems. Biochem Soc Trans 33:331–334CrossRefGoogle Scholar
  56. Qu H, Ricklin D, Lambris JD (2009) Recent developments in low molecular weight complement inhibitors. Mol Immunol 47:185–195CrossRefPubMedPubMedCentralGoogle Scholar
  57. Rawlings ND, Tolle DP, Barret AJ (2004) Evolutionary families of peptidase inhibitors. Biochem J 378:705–716CrossRefPubMedPubMedCentralGoogle Scholar
  58. Ricklin D, Lambris JD (2007) Complement-targeted therapeutics. Nat Biotechnol 25:1265–1275CrossRefPubMedPubMedCentralGoogle Scholar
  59. Ricklin D, Hajishengallis G, Yang K, Lambris JD (2010) Complement: a key system for immune surveillance and homeostasis. Nat Immunol 11:785–797CrossRefPubMedPubMedCentralGoogle Scholar
  60. Rossi V, Bally I, Thielens NM, Esser AF, Arlaud GJ (1998) Baculovirus-mediated expression of truncated modular fragments from the catalytic region of human complement serine protease C1s. Evidence for the involvement of both complement control protein modules in the recognition of the C4 protein substrate. J Biol Chem 273:1232–1239CrossRefGoogle Scholar
  61. Rossi V, Cseh S, Bally I, Thielens NM, Jensenius JC, Arlaud GJ (2001) Substrate specificities of recombinant mannan-binding lectin-associated serine proteases-1 and -2. J Biol Chem 276:40880–40887CrossRefGoogle Scholar
  62. Rossi V, Bally I, Ancelet S, Xu Y, Frémeaux-Bacchi V, Vivès RR, Sadir R, Thielens N, Arlaud GJ (2010) Functional characterization of the recombinant human C1 inhibitor serpin domain: insights into heparin binding. J Immunol 184:4982–4989CrossRefGoogle Scholar
  63. Roy A, Kucukural A, Zhang Y (2010) I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc 5:725–738CrossRefPubMedPubMedCentralGoogle Scholar
  64. Ruiz-Gómez G, Lim J, Halili MA, Le GT, Madala PK, Abbenante G, Fairlie DP (2009) Structure-activity relationships for substrate-based inhibitors of human complement factor B. J Med Chem 52:6042–6052CrossRefPubMedPubMedCentralGoogle Scholar
  65. Sardana N, Craig TJ (2011) Recent advances in management and treatment of hereditary angioedema. Pediatrics 128:1173–1180CrossRefPubMedPubMedCentralGoogle Scholar
  66. Schwaeble WJ, Lynch NJ, Clark JE, Marber M, Samani NJ, Ali YM, Dudler T, Parent B, Lhotta K, Wallis R, Farrar CA, Sacks S, Lee H, Zhang M, Iwaki D, Takahashi M, Fujita T, Tedford CE, Stover CM (2011) Targeting of mannan-binding lectin-associated serine protease-2 confers protection from myocardial and gastrointestinal ischemia/reperfusion injury. Proc Natl Acad Sci USA 108:7523–7528CrossRefPubMedPubMedCentralGoogle Scholar
  67. Schwertz H, Carter JM, Russ M, Schubert S, Schlitt A, Buerke U, Schmidt M, Hillen H, Werdan K, Buerke M (2008) Serine protease inhibitor nafamostat given before reperfusion reduces inflammatory myocardial injury by complement and neutrophil inhibition. J Cardiovasc Pharmacol 52:151–160CrossRefPubMedPubMedCentralGoogle Scholar
  68. Scott CJ, Taggart CC (2010) Biologic protease inhibitors as novel therapeutic agents. Biochimie 92:1681–1688CrossRefPubMedPubMedCentralGoogle Scholar
  69. Silverman GA, Bird PI, Carrell RW, Church FC, Coughlin PB, Gettins PG, Irving JA, Lomas DA, Luke CJ, Moyer RW, Pemberton PA, Remold-O’Donnell E, Salvesen GS, Travis J, Whisstock JC (2001) The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. J Biol Chem 276:33293–33296CrossRefPubMedPubMedCentralGoogle Scholar
  70. Sim RB, Tsiftsoglou SA (2004) Proteases of the complement system. Biochem Soc Trans 32:21–27CrossRefPubMedPubMedCentralGoogle Scholar
  71. Skjoedt MO, Hummelshoj T, Palarasah Y, Honore C, Koch C, Skjodt K, Garred P (2010a) A novel mannose-binding lectin/ficolin-associated protein is highly expressed in heart and skeletal muscle tissues and inhibits complement activation. J Biol Chem 285:8234–8243CrossRefPubMedPubMedCentralGoogle Scholar
  72. Skjoedt MO, Palarasah Y, Munthe-Fog L, Jie Ma Y, Weiss G, Skjodt K, Koch C, Garred P (2010b) MBL-associated serine protease-3 circulates in high serum concentrations predominantly in complex with Ficolin-3 and regulates Ficolin-3 mediated complement activation. Immunobiology 215:921–931CrossRefGoogle Scholar
  73. Sottrup-Jensen L (1989) Alpha-macroglobulins: structure, shape, and mechanism of proteinase complex formation. J Biol Chem 264:11539–11542PubMedGoogle Scholar
  74. Stover CM, Thiel S, Thelen M, Lynch NJ, Vorup-Jensen T, Jensenius JC, Schwaeble WJ (1999) Two constituents of the initiation complex of the mannan-binding lectin activation pathway of complement are encoded by a single structural gene. J Immunol 162:3481–3490Google Scholar
  75. Szalai AJ, Digerness SB, Agrawal A, Kearney JF, Bucy RP, Niwas S, Kilpatrick JM, Babu YS, Volanakis JE (2000) The Arthus reaction in rodents: species-specific requirement of complement. J Immunol 164:463–468CrossRefGoogle Scholar
  76. Tagawa T (2011) Protease inhibitor nafamostat mesilate attenuates complement activation and improves function of xenografts in a discordant lung perfusion model. Xenotransplantation 18:315–319CrossRefGoogle Scholar
  77. Takahashi M, Endo Y, Fujita T, Matsushita M (1999) A truncated form of mannose-binding lectin-associated serine protease (MASP)-2 expressed by alternative polyadenylation is a component of the lectin complement pathway. Int Immunol 11:859–863CrossRefGoogle Scholar
  78. Takahashi M, Iwaki D, Kanno K, Ishida Y, Xiong J, Matsushita M, Endo Y, Miura S, Ishii N, Sugamura K, Fujita T (2008) Mannose-binding lectin (MBL)-associated serine protease (MASP)-1 contributes to activation of the lectin complement pathway. J Immunol 180:6132–6138CrossRefGoogle Scholar
  79. Takahashi M, Ishida Y, Iwaki D, Kanno K, Suzuki T, Endo Y, Homma Y, Fujita T (2010) Essential role of mannose-binding lectin-associated serine protease-1 in activation of the complement factor D. J Exp Med 207:29–37CrossRefPubMedPubMedCentralGoogle Scholar
  80. Thiel S (2007) Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins and associated proteins. Mol Immunol 44:3875–3888CrossRefGoogle Scholar
  81. Travins JM, Ali F, Huang H, Ballentine SK, Khalil E, Hufnagel HR, Pan W, Gushue J, Leonard K, Bone RF, Soll RM, DesJarlais RL, Crysler CS, Ninan N, Kirkpatrick J, Cummings MD, Huebert N, Molloy CJ, Gaul M, Tomczuk BE, Subasinghe NL (2008) Biphenylsulfonyl-thiophene-carboxamidine inhibitors of the complement component C1s. Bioorg Med Chem Lett 18:1603–1606CrossRefGoogle Scholar
  82. Volanakis JE, Narayana SV (1996) Complement factor D, a novel serine protease. Protein Sci 5:553–564CrossRefPubMedPubMedCentralGoogle Scholar
  83. Vorup-Jensen T, Petersen SV, Hansen AG, Poulsen K, Schwaeble W, Sim RB, Reid KB, Davis SJ, Thiel S, Jensenius JC (2000) Distinct pathways of mannan-binding lectin (MBL)- and C1-complex autoactivation revealed by reconstitution of MBL with recombinant MBL-associated serine protease-2. J Immunol 165:2093–2100CrossRefGoogle Scholar
  84. Walport MJ (2001) Complement. First of two parts. N Engl J Med 344:1058–1066CrossRefGoogle Scholar
  85. Walsh MC, Bourcier T, Takahashi K, Shi L, Busche MN, Rother RP, Solomon SD, Ezekowitz RA, Stahl GL (2005) Mannose-binding lectin is a regulator of inflammation that accompanies myocardial ischemia and reperfusion injury. J Immunol 175:541–546CrossRefPubMedPubMedCentralGoogle Scholar
  86. Whisstock JC, Silverman GA, Bird PI, Bottomley SP, Kaiserman D, Luke CJ, Pak SC, Reichhart JM, Huntington JA (2010) Serpins flex their muscle: II. Structural insights into target peptidase recognition, polymerization, and transport functions. J Biol Chem 285:24307–24312CrossRefPubMedPubMedCentralGoogle Scholar
  87. Wu Y, Eigenbrot C, Liang WC, Stawicki S, Shia S, Fan B, Ganesan R, Lipari MT, Kirchhofer D (2007) Structural insight into distinct mechanisms of protease inhibition by antibodies. Proc Natl Acad Sci USA 104:19784–19789CrossRefGoogle Scholar
  88. Zani M-L, Moreau T (2010) Phage display as a powerful tool to engineer protease inhibitors. Biochemie 92:1689–1704CrossRefGoogle Scholar
  89. Ziccardi R (1985) Demonstration of the interaction of native C1 with monomeric immunoglobulins and C1 inhibitor. J Immunol 134:2559–2563PubMedGoogle Scholar
  90. Zundel S, Cseh S, Lacroix M, Dahl MR, Matsushita M, Andrieu JP, Schwaeble WJ, Jensenius JC, Fujita T, Arlaud GJ, Thielens NM (2004) Characterization of recombinant mannan-binding lectin-associated serine protease (MASP)-3 suggests an activation mechanism different from that of MASP-1 and MASP-2. J Immunol 172:4342–4350CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Péter Gál
    • 1
    Email author
  • József Dobó
    • 1
  • László Beinrohr
    • 1
  • Gábor Pál
    • 2
  • Péter Závodszky
    • 1
  1. 1.Institute of Enzymology, Research Centre for Natural SciencesHungarian Academy of SciencesBudapestHungary
  2. 2.Department of BiochemistryEötvös Loránd UniversityBudapestHungary

Personalised recommendations