Table of Contents
Journal of Amino Acids
Volume 2011 (2011), Article ID 606797, 10 pages
http://dx.doi.org/10.4061/2011/606797
Review Article

Serpin Inhibition Mechanism: A Delicate Balance between Native Metastable State and Polymerization

1Department of Biosciences, Jamia Millia Islamia University, Jamia Nagar, New Delhi 110025, India
2Department of Biotechnology, National Institute of Technology Calicut (NITC), NIT Campus P.O., Calicut, Kerala 673601, India

Received 14 February 2011; Accepted 7 March 2011

Academic Editor: Zulfiqar Ahmad

Copyright © 2011 Mohammad Sazzad Khan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. W. Carrell, P. A. Pemberton, and D. R. Boswell, “The serpins: evolution and adaptation in a family of protease inhibitors,” Cold Spring Harbor Symposia on Quantitative Biology, vol. 52, pp. 527–535, 1987. View at Google Scholar · View at Scopus
  2. P. G. W. Gettins, “Keeping the serpin machine running smoothly,” Genome Research, vol. 10, no. 12, pp. 1833–1835, 2000. View at Publisher · View at Google Scholar · View at Scopus
  3. J. A. Huntington, R. J. Read, and R. W. Carrell, “Structure of a serpin-protease complex shows inhibition by deformation,” Nature, vol. 407, no. 6806, pp. 923–926, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. P. A. Patston, “Serpins and other serine protease inhibitors,” Immunology Today, vol. 21, no. 7, p. 354, 2000. View at Publisher · View at Google Scholar · View at Scopus
  5. J. Potempa, E. Korzus, and J. Travis, “The serpin superfamily of proteinase inhibitors: structure, function, and regulation,” Journal of Biological Chemistry, vol. 269, no. 23, pp. 15957–15960, 1994. View at Google Scholar · View at Scopus
  6. P. G. W. Gettins, “Serpin structure, mechanism, and function,” Chemical Reviews, vol. 102, no. 12, pp. 4751–4804, 2002. View at Publisher · View at Google Scholar · View at Scopus
  7. J. A. Irving, R. N. Pike, A. M. Lesk, and J. C. Whisstock, “Phylogeny of the serpin superfamily: implications of patterns of amino acid conservation for structure and function,” Genome Research, vol. 10, no. 12, pp. 1845–1864, 2000. View at Publisher · View at Google Scholar · View at Scopus
  8. G. A. Silverman, P. I. Bird, R. W. Carrell et al., “The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature,” Journal of Biological Chemistry, vol. 276, no. 36, pp. 33293–33296, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  9. A. J. Horvath, J. A. Irving, J. Rossjohn et al., “The murine orthologue of human antichymotrypsin: a structural paradigm for clade A3 serpins,” Journal of Biological Chemistry, vol. 280, no. 52, pp. 43168–43178, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. J. C. Whisstock, R. Skinner, R. W. Carrell, and A. M. Lesk, “Conformational changes in serpins: I. The native and cleaved conformations of α-antitrypsin,” Journal of Molecular Biology, vol. 295, no. 3, pp. 651–665, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. D. A. Lawrence, S. T. Olson, S. Palaniappan, and D. Ginsburg, “Serpin reactive center loop mobility is required for inhibitor function but not for enzyme recognition,” Journal of Biological Chemistry, vol. 269, no. 44, pp. 27657–27662, 1994. View at Google Scholar · View at Scopus
  12. W. S. W. Chang, M. R. Wardell, D. A. Lomas, and R. W. Carrell, “Probing serpin reactive-loop conformations by proteolytic cleavage,” Biochemical Journal, vol. 314, no. 2, pp. 647–653, 1996. View at Google Scholar · View at Scopus
  13. R. W. Carrell, P. E. Stein, G. Fermi, and M. R. Wardell, “Biological implications of a 3 Å structure of dimeric antithrombin,” Structure, vol. 2, no. 4, pp. 257–270, 1994. View at Google Scholar · View at Scopus
  14. J. O. Jeppsson, “Amino acid substitution Glu leads to Lys alpha1-antitrypsin,” Federation of European Biological Society Letters, vol. 65, no. 2, pp. 195–197, 1976. View at Google Scholar
  15. P. E. Stein and R. W. Carrell, “What do dysfunctional serpins tell us about molecular mobility and disease?” Nature Structural Biology, vol. 2, no. 2, pp. 96–113, 1995. View at Publisher · View at Google Scholar · View at Scopus
  16. M. M. Krem and E. Di Cera, “Conserved Ser residues, the shutter region, and speciation in serpin evolution,” Journal of Biological Chemistry, vol. 278, no. 39, pp. 37810–37814, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. J. Mottonen, A. Strand, J. Symersky et al., “Structural basis of latency in plasminogen activator inhibitor-1,” Nature, vol. 355, no. 6357, pp. 270–273, 1992. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. M. A. Dunstone, W. Dai, J. C. Whisstock et al., “Cleaved antitrypsin polymers at atomic resolution,” Protein Science, vol. 9, no. 2, pp. 417–420, 2000. View at Google Scholar · View at Scopus
  19. P. A. Patston, F. C. Church, and S. T. Olson, “Serpin-ligand interactions,” Methods, vol. 32, no. 2, pp. 93–109, 2004. View at Publisher · View at Google Scholar · View at Scopus
  20. A. Jayakumar, Y. Kang, M. J. Frederick et al., “Inhibition of the cysteine proteinases cathepsins K and L by the serpin headpin (SERPINB13): a kinetic analysis,” Archives of Biochemistry and Biophysics, vol. 409, no. 2, pp. 367–374, 2003. View at Publisher · View at Google Scholar · View at Scopus
  21. M. C. Naski, D. A. Lawrence, D. F. Mosher, T. J. Podor, and D. Ginsburg, “Kinetics of inactivation of α-thrombin by plasminogen activator inhibitor-1. Comparison of the effects of native and urea-treated forms of vitronectin,” Journal of Biological Chemistry, vol. 268, no. 17, pp. 12367–12372, 1993. View at Google Scholar · View at Scopus
  22. M. A. Jairajpuri, A. Lu, and S. C. Bock, “Elimination of P1 arginine 393 interaction with underlying glutamic acid 255 partially activates antithrombin III for thrombin inhibition but not factor Xa inhibition,” Journal of Biological Chemistry, vol. 277, no. 27, pp. 24460–24465, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  23. M. A. Jairajpuri, A. Lu, U. Desai, S. T. Olson, I. Bjork, and S. C. Bock, “Antithrombin III phenylalanines 122 and 121 contribute to its high affinity for heparin and its conformational activation,” Journal of Biological Chemistry, vol. 278, no. 18, pp. 15941–15950, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. R. W. Carrell and P. E. Stein, “The biostructural pathology of the serpins: critical function of sheet opening mechanism,” Biological Chemistry Hoppe-Seyler, vol. 377, no. 1, pp. 1–17, 1996. View at Google Scholar · View at Scopus
  25. J. C. Whisstock and S. P. Bottomley, “Molecular gymnastics: serpin structure, folding and misfolding,” Current Opinion in Structural Biology, vol. 16, no. 6, pp. 761–768, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. H. Im, M. S. Woo, K. Y. Hwang, and M. H. Yu, “Interactions causing the kinetic trap in serpin protein folding,” Journal of Biological Chemistry, vol. 277, no. 48, pp. 46347–46354, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. E. Marszal and A. Shrake, “Serpin crystal structure and serpin polymer structure,” Archives of Biochemistry and Biophysics, vol. 453, no. 1, pp. 123–129, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. C. M. Hekman and D. J. Loskutoff, “Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants,” Journal of Biological Chemistry, vol. 260, no. 21, pp. 11581–11587, 1985. View at Google Scholar · View at Scopus
  29. R. W. Carrell, J. A. Huntington, A. Mushunje, and A. Zhou, “The conformational basis of thrombosis,” Thrombosis and Haemostasis, vol. 86, no. 1, pp. 14–22, 2001. View at Google Scholar · View at Scopus
  30. H. Tonie Wright and M. A. Blajchman, “Proteolytically cleaved mutant antithrombin-Hamilton has high stability to denaturation characteristic of wild type inhibitor serpins,” FEBS Letters, vol. 348, no. 1, pp. 14–16, 1994. View at Publisher · View at Google Scholar
  31. M. Yamasaki, Y. Mikami, and M. B. Hirose, “Loop-inserted and thermostabilized structure of P1-P1′ cleaved ovalbumin mutant R339T,” Journal of Molecular Biology, vol. 315, no. 2, pp. 113–120, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. P. Gettins and B. Harten, “Properties of thrombin- and elastase-modified human antithrombin III,” Biochemistry, vol. 27, no. 10, pp. 3634–3639, 1988. View at Google Scholar · View at Scopus
  33. A. J. Schulze, U. Baumann, S. Knof, E. Jaeger, R. Huber, and C. B. Laurell, “Structural transition of α-antitrypsin by a peptide sequentially similar to β-strand s4A,” European Journal of Biochemistry, vol. 194, no. 1, pp. 51–56, 1990. View at Publisher · View at Google Scholar · View at Scopus
  34. T. R. Dafforn, R. N. Pike, and S. P. Bottomley, “Physical characterization of serpin conformations,” Methods, vol. 32, no. 2, pp. 150–158, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. G. L. Devlin and S. P. Bottomley, “A protein family under 'stress'—serpin stability, folding and misfolding,” Frontiers in Bioscience, vol. 10, no. 1, pp. 288–299, 2005. View at Google Scholar · View at Scopus
  36. E. J. Seo, H. Im, J. S. Maeng, K. E. Kim, and M. H. Yu, “Distribution of the native strain in human α-antitrypsin and its association with protease inhibitor function,” Journal of Biological Chemistry, vol. 275, no. 22, pp. 16904–16909, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. J. L. Sohl, S. S. Jaswal, and D. A. Agard, “Unfolded conformations of α-lytic protease are more stable than its native state,” Nature, vol. 395, no. 6704, pp. 817–819, 1998. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. K. N. Lee, S. D. Park, and M. H. Yu, “Probing the native strain in α-antitrypsin,” Nature Structural Biology, vol. 3, no. 6, pp. 497–500, 1996. View at Publisher · View at Google Scholar · View at Scopus
  39. S. E. Ryu, H. J. Choi, K. S. Kwon, K. N. Lee, and M. H. Yu, “The native strains in the hydrophobic core and flexible reactive loop of a serine protease inhibitor: crystal structure of an uncleaved α-antitrypsin at 2.7 Å,” Structure, vol. 4, no. 10, pp. 1181–1192, 1996. View at Google Scholar · View at Scopus
  40. H. Im, E. J. Seo, and M. H. Yu, “Metastability in the inhibitory mechanism of human α-antitrypsin,” Journal of Biological Chemistry, vol. 274, no. 16, pp. 11072–11077, 1999. View at Publisher · View at Google Scholar · View at Scopus
  41. K. N. Lee, C. S. Lee, W. C. Tae, K. W. Jackson, V. J. Christiansen, and P. A. McKee, “Cross-linking of wild-type and mutant α-antiplasmins to by activated factor XIII and by a tissue transglutaminase,” Journal of Biological Chemistry, vol. 275, no. 48, pp. 37382–37389, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. D. J. Tew and S. P. Bottomley, “Probing the equilibrium denaturation of the serpin α-antitrypsin with single tryptophan mutants; Evidence for structure in the urea unfolded state,” Journal of Molecular Biology, vol. 313, no. 5, pp. 1161–1169, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  43. L. D. Cabrita, J. C. Whisstock, and S. P. Bottomley, “Probing the role of the F-helix in serpin stability through a single tryptophan substitution,” Biochemistry, vol. 41, no. 14, pp. 4575–4581, 2002. View at Publisher · View at Google Scholar · View at Scopus
  44. L. D. Cabrita and S. P. Bottomley, “How do proteins avoid becoming too stable? Biophysical studies into metastable proteins,” European Biophysics Journal, vol. 33, no. 2, pp. 83–88, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  45. H. Im, M. J. Ryu, and M. H. Yu, “Engineering thermostability in serine protease inhibitors,” Protein Engineering, Design and Selection, vol. 17, no. 4, pp. 325–331, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  46. M. Bruch, V. Weiss, and J. Engel, “Plasma serine proteinase inhibitors (serpins) exhibit major conformational changes and a large increase in conformational stability upon cleavage at their reactive sites,” Journal of Biological Chemistry, vol. 263, no. 32, pp. 16626–16630, 1988. View at Google Scholar · View at Scopus
  47. K. E. Pedersen, A. P. Einholm, A. Christensen et al., “Plasminogen activator inhibitor-1 polymers, induced by inactivating amphipathic organochemical ligands,” Biochemical Journal, vol. 372, no. 3, pp. 747–755, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. H. Im and M. H. Yu, “Role of Lys335 in the metastability and function of inhibitory serpins,” Protein Science, vol. 9, no. 5, pp. 934–941, 2000. View at Google Scholar · View at Scopus
  49. D. A. Lomas, D. L. Evans, J. T. Finch, and R. W. Carrell, “The mechanism of Z α-antitrypsin accumulation in the liver,” Nature, vol. 357, no. 6379, pp. 605–607, 1992. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. D. A. Lomas, D. L. Evans, C. Upton, G. McFadden, and R. W. Carrell, “Inhibition of plasmin, urokinase, tissue plasminogen activator, and C(1S) by a myxoma virus serine proteinase inhibitor,” Journal of Biological Chemistry, vol. 268, no. 1, pp. 516–521, 1993. View at Google Scholar · View at Scopus
  51. E. Miranda and D. A. Lomas, “Neuroserpin: a serpin to think about,” Cellular and Molecular Life Sciences, vol. 63, no. 6, pp. 709–722, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  52. R. L. Davis, A. E. Shrimpton, P. D. Holohan et al., “Familial dementia caused by polymerization of mutant neuroserpin,” Nature, vol. 401, no. 6751, pp. 376–379, 1999. View at Publisher · View at Google Scholar · View at Scopus
  53. R. L. Davis, A. E. Shrimpton, R. W. Carrell et al., “Association between conformational mutations in neuroserpin and onset and severity of dementia,” Lancet, vol. 359, no. 9325, pp. 2242–2247, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  54. T. Nakagawa, T. Kubota, M. Kabuto et al., “Production of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 by human brain tumors,” Journal of Neurosurgery, vol. 81, no. 1, pp. 69–77, 1994. View at Google Scholar · View at Scopus
  55. M. A. Dunstone, W. Dai, J. C. Whisstock et al., “Cleaved antitrypsin polymers at atomic resolution,” Protein Science, vol. 9, no. 2, pp. 417–420, 2000. View at Google Scholar · View at Scopus
  56. B. Gooptu and D. A. Lomas, “Conformational pathology of the serpins: themes, variations, and therapeutic strategies,” Annual Review of Biochemistry, vol. 78, pp. 147–176, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  57. D. A. Lomas, P. R. Elliott, W. S. W. Chang, M. R. Wardell, and R. W. Carrell, “Preparation and characterization of latent α-antitrypsin,” Journal of Biological Chemistry, vol. 270, no. 10, pp. 5282–5288, 1995. View at Publisher · View at Google Scholar · View at Scopus
  58. A. E. Mast, J. J. Enghild, and G. Salvesen, “Conformation of the reactive site loop of α-proteinase inhibitor probed by limited proteolysis,” Biochemistry, vol. 31, no. 10, pp. 2720–2728, 1992. View at Google Scholar · View at Scopus
  59. P. Sivasothy, T. R. Dafforn, P. G. W. Gettins, and D. A. Lomas, “Pathogenic α-antitrypsin polymers are formed by reactive loop-β-sheet A linkage,” Journal of Biological Chemistry, vol. 275, no. 43, pp. 33663–33668, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  60. H. Koloczek, A. Banbula, G. S. Salvesen, and J. Potempa, “Serpin αproteinase inhibitor probed by intrinsic tryptophan fluorescence spectroscopy,” Protein Science, vol. 5, no. 11, pp. 2226–2235, 1996. View at Google Scholar · View at Scopus
  61. A. M. Sharp, P. E. Stein, N. S. Pannu et al., “The active conformation of plasminogen activator inhibitor 1, a target for drugs to control fibrinolysis and cell adhesion,” Structure, vol. 7, no. 2, pp. 111–118, 1999. View at Publisher · View at Google Scholar · View at Scopus
  62. E. Marszal, D. Danino, and A. Shrake, “A novel mode of polymerization of α-proteinase inhibitor,” Journal of Biological Chemistry, vol. 278, no. 22, pp. 19611–19618, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  63. P. Singh and M. A. Jairajpuri, “Strand 6B deformation and residues exposure towards N-terminal end of helix B during proteinase inhibition by Serpins,” Bioinformation, vol. 5, no. 8, pp. 315–319, 2011. View at Google Scholar