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Gene Review

PTI  -  pancreatic trypsin inhibitor

Bos taurus

Synonyms: BPI, BPTI
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Disease relevance of PTI

  • The cDNA for bovine spleen trypsin inhibitor (SI), a homologue of bovine pancreatic trypsin inhibitor (BPTI), including the natural mammalian presequence was expressed in tobacco using Agrobacterium tumefaciens-mediated transformation [1].
  • However, when expressed at 37 degrees C in E. coli, or when refolded at 37 degrees or 52 degrees C in vitro, the mutant proteins folded readily into the native conformation, albeit at a rate somewhat slower than that exhibited by wild-type BPTI [2].
  • In addition, we describe the results of calculations of C(alpha), C(beta), C(gamma)1, C(gamma)2, and C(delta) shifts in the two isoleucine residues in bovine pancreatic trypsin inhibitor and the four isoleucines in a cytochrome c and demonstrate that the side chain chemical shifts are strongly influenced by chi(2) torsion angle effects [3].
  • The potential of BPIP for the treatment of pestivirus and hepacivirus infections is discussed [4].
  • BPIP was inactive against the hepatitis C virus subgenomic replicon and yellow fever virus but demonstrated weak activity against GB virus [4].

Psychiatry related information on PTI


High impact information on PTI


Chemical compound and disease context of PTI

  • In particular, the BPTI produced by E. coli had three disulfide bonds that appeared to be identical to those found in native BPTI, as assayed by sensitivity to iodoacetate, dithiothreitol, and urea [11].
  • A mutant of bovine pancreatic trypsin inhibitor (BPTI) has been constructed and expressed in Escherichia coli in order to probe the kinetic and structural consequences of truncating the binding loop residues to alanine [12].
  • A recombinant model of the reduced state of BPTI, called [R]Ala, in which all six Cys residues are replaced with Ala, has been expressed in Escherichia coli [13].
  • From the linear correlation between these two parameters it was found that 5 out of the 6 tested aprotinin analogues, rTAP and r-hirudin completely inhibited thrombus formation at a therapeutical (2- to 3-fold) aPTT prolongation while 4C2, heparin and enoxaparin only inhibited thrombus formation for 40 to 50 percent at a 2-fold aPTT prolongation [14].
  • A combination of aprotinin with tranexamic acid may be effective in preventing or delaying rebleeding after rupture of an intracerebral aneurysm; the addition of aprotinin seems to decrease the incidence of delayed cerebral vasospasm and ischaemic complications which are sometimes noted when tranexamic acid alone is used [15].

Biological context of PTI

  • Unique-sequence synthetic DNA probes, based on the known amino acid sequence of bovine pancreatic trypsin inhibitor, were constructed from oligodeoxynucleotides [16].
  • DNA sequence analysis of this clone indicated that the BPTI coding region was neither preceded by a start codon nor immediately followed by a termination codon [16].
  • A synthetic probe also was used to isolate a cloned BPTI gene from a bovine genomic library [16].
  • The largest changes as a result of pressure are in the loop 10-16, which contains the active site of BPTI, and residues 38-42, which are adjacent to buried water molecules [17].
  • A synthetic gene encoding the protein sequence of mature bovine pancreatic trypsin inhibitor (BPTI) has been cloned into a novel E. coli expression vector [18].

Anatomical context of PTI


Associations of PTI with chemical compounds


Physical interactions of PTI

  • Aprotinin did not inhibit [3H]5'-guanylylimidodiphosphate binding to FSH receptor-enriched membranes, suggesting that its effects on the affinity of the receptor for FSH and on AC activation were not mediated through an interaction with FSH receptor-associated G-protein [25].
  • CONCLUSIONS: A 3-dimensional capillary network can be induced in aprotinin-stabilized FG using FGF-1 or VEGF with synergism between the 2 angiogens [26].

Enzymatic interactions of PTI

  • 5. Solutions of aprotinin, modified aprotinin with the Lys15-Ala16 peptide bond cleaved and mixtures of both species were incubated with 10 mol% porcine beta-trypsin [27].

Regulatory relationships of PTI


Other interactions of PTI

  • SI was found to exist as two forms, one coinciding with authentic BPTI on western blots and the second marginally larger due to retention of the C-terminal peptide [1].
  • To demonstrate the scope of the methods, MD simulations of two proteins, PTI and ubiquitin, were performed [31].
  • Both aprotinin, an inhibitor of plasmin, and anti-urokinase type PA IgG blocked the generation of active TGF-beta in cultures exposed to bFGF [32].
  • These include poly(L-alanine) representatives of minima corresponding to secondary and supersecondary structures, as well as poly(L-alanine) images for tertiary structures of the naturally occurring proteins bovine pancreatic trypsin inhibitor, crambin, ribonuclease A, and superoxide dismutase [33].
  • Since kallikrein is an arginine-directed serine protease, we hypothesized that an altered form of aprotinin, Arg15-aprotinin, might be a better inhibitor [34].

Analytical, diagnostic and therapeutic context of PTI


  1. The expression of a mammalian proteinase inhibitor, bovine spleen trypsin inhibitor in tobacco and its effects on Helicoverpa armigera larvae. Christeller, J.T., Burgess, E.P., Mett, V., Gatehouse, H.S., Markwick, N.P., Murray, C., Malone, L.A., Wright, M.A., Philip, B.A., Watt, D., Gatehouse, L.N., Lövei, G.L., Shannon, A.L., Phung, M.M., Watson, L.M., Laing, W.A. Transgenic Res. (2002) [Pubmed]
  2. Mutants of bovine pancreatic trypsin inhibitor lacking cysteines 14 and 38 can fold properly. Marks, C.B., Naderi, H., Kosen, P.A., Kuntz, I.D., Anderson, S. Science (1987) [Pubmed]
  3. Carbon-13 NMR shielding in the twenty common amino acids: comparisons with experimental results in proteins. Sun, H., Sanders, L.K., Oldfield, E. J. Am. Chem. Soc. (2002) [Pubmed]
  4. A novel, highly selective inhibitor of pestivirus replication that targets the viral RNA-dependent RNA polymerase. Paeshuyse, J., Leyssen, P., Mabery, E., Boddeker, N., Vrancken, R., Froeyen, M., Ansari, I.H., Dutartre, H., Rozenski, J., Gil, L.H., Letellier, C., Lanford, R., Canard, B., Koenen, F., Kerkhofs, P., Donis, R.O., Herdewijn, P., Watson, J., De Clercq, E., Puerstinger, G., Neyts, J. J. Virol. (2006) [Pubmed]
  5. Kunitz-type protease inhibitor found in rat mast cells. Purification, properties, and amino acid sequence. Kido, H., Yokogoshi, Y., Katunuma, N. J. Biol. Chem. (1988) [Pubmed]
  6. Carbohydrate-containing derivatives of the trypsin-kallikrein inhibitor aprotinin from bovine organs. I. Modification with lactose, characterization and behaviour of the preparation in vivo. Larionova, N.I., Mityushina, G.V., Kazanskaya, N.F., Blidchenko, Y.A., Berezin, I.V. Hoppe-Seyler's Z. Physiol. Chem. (1984) [Pubmed]
  7. The pro region of BPTI facilitates folding. Weissman, J.S., Kim, P.S. Cell (1992) [Pubmed]
  8. Fibrinogen degradation product fragment D induces endothelial cell detachment by activation of cell-mediated fibrinolysis. Ge, M., Tang, G., Ryan, T.J., Malik, A.B. J. Clin. Invest. (1992) [Pubmed]
  9. A human lung mast cell chymotrypsin-like enzyme. Identification and partial characterization. Wintroub, B.U., Kaempfer, C.E., Schechter, N.M., Proud, D. J. Clin. Invest. (1986) [Pubmed]
  10. Evidence of normal functional levels of activated protein C inhibitor in combined Factor V/VIII deficiency disease. Canfield, W.M., Kisiel, W. J. Clin. Invest. (1982) [Pubmed]
  11. Production of native, correctly folded bovine pancreatic trypsin inhibitor by Escherichia coli. Marks, C.B., Vasser, M., Ng, P., Henzel, W., Anderson, S. J. Biol. Chem. (1986) [Pubmed]
  12. High-resolution structure of bovine pancreatic trypsin inhibitor with altered binding loop sequence. Czapinska, H., Otlewski, J., Krzywda, S., Sheldrick, G.M., Jaskólski, M. J. Mol. Biol. (2000) [Pubmed]
  13. Formation of a hydrophobic cluster in denatured bovine pancreatic trypsin inhibitor. Lumb, K.J., Kim, P.S. J. Mol. Biol. (1994) [Pubmed]
  14. Characterisation of a novel series of aprotinin-derived anticoagulants. II. Comparative antithrombotic effects on primary thrombus formation in vivo. Stassen, J.M., Lambeir, A.M., Vreys, I., Deckmyn, H., Matthyssens, G., Nyström, A., Vermylen, J. Thromb. Haemost. (1995) [Pubmed]
  15. Clinical application of inhibitors of fibrinolysis. Verstraete, M. Drugs (1985) [Pubmed]
  16. Isolation of a genomic clone for bovine pancreatic trypsin inhibitor by using a unique-sequence synthetic DNA probe. Anderson, S., Kingston, I.B. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  17. The solution structure of bovine pancreatic trypsin inhibitor at high pressure. Williamson, M.P., Akasaka, K., Refaee, M. Protein Sci. (2003) [Pubmed]
  18. A synthetic operon containing 14 bovine pancreatic trypsin inhibitor genes is expressed in E. coli. von Wilcken-Bergmann, B., Tils, D., Sartorius, J., Auerswald, E.A., Schröder, W., Müller-Hill, B. EMBO J. (1986) [Pubmed]
  19. Presence of pancreatic trypsin inhibitor in adrenal medullary chromaffin cells. Lewis, R.V., Ray, P., Coguill, R., Kruggel, W. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  20. Purification of a novel serpin-like protein from bovine brain. Nishibori, M., Chikai, T., Kawabata, M., Ohta, J., Ubuka, T., Saeki, K. Neurosci. Res. (1995) [Pubmed]
  21. Effects of protease inhibitors and substrates on motility of mammalian spermatozoa. de Lamirande, E., Gagnon, C. J. Cell Biol. (1986) [Pubmed]
  22. Isolation of pancreatic trypsin inhibitor from bovine pituitary glands. Li, C.H., Chung, D. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  23. Genetic dissection of pancreatic trypsin inhibitor. Goldenberg, D.P., Berger, J.M., Laheru, D.A., Wooden, S., Zhang, J.X. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  24. Proteolytic activity of the purified hormone-binding subunit in the estrogen receptor. Molinari, A.M., Abbondanza, C., Armetta, I., Medici, N., Minucci, S., Moncharmont, B., Nigro, V., Puca, G.A. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  25. The effects of aprotinin on follicle-stimulating hormone binding and signal transduction in bovine calf testis. Grasso, P., Reichert, L.E. Endocrinology (1989) [Pubmed]
  26. Angiogenic effect of fibroblast growth factor-1 and vascular endothelial growth factor and their synergism in a novel in vitro quantitative fibrin-based 3-dimensional angiogenesis system. Xue, L., Greisler, H.P. Surgery (2002) [Pubmed]
  27. The pH dependence of the equilibrium constant KHyd for the hydrolysis of the Lys15-Ala16 reactive-site peptide bond in bovine pancreatic trypsin inhibitor (aprotinin). Siekmann, J., Wenzel, H.R., Matuszak, E., von Goldammer, E., Tschesche, H. J. Protein Chem. (1988) [Pubmed]
  28. The preparation and properties of bovine enterokinase. Liepnieks, J.J., Light, A. J. Biol. Chem. (1979) [Pubmed]
  29. Human eccrine sweat contains tissue kallikrein and kininase II. Hibino, T., Takemura, T., Sato, K. J. Invest. Dermatol. (1994) [Pubmed]
  30. Staphylococcus aureus stimulates urokinase-type plasminogen activator expression by bovine mammary cells. Zavizion, B., White, J.H., Bramley, A.J. J. Infect. Dis. (1997) [Pubmed]
  31. Quantification and visualization of molecular surface flexibility. Zachmann, C.D., Kast, S.M., Brickmann, J. Journal of molecular graphics. (1995) [Pubmed]
  32. Basic fibroblast growth factor-induced activation of latent transforming growth factor beta in endothelial cells: regulation of plasminogen activator activity. Flaumenhaft, R., Abe, M., Mignatti, P., Rifkin, D.B. J. Cell Biol. (1992) [Pubmed]
  33. Poly(L-alanine) as a universal reference material for understanding protein energies and structures. Head-Gordon, T., Stillinger, F.H., Wright, M.H., Gay, D.M. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  34. Kinetics of inhibition of human plasma kallikrein by a site-specific modified inhibitor Arg15-aprotinin: evaluation using a microplate system and comparison with other proteases. Scott, C.F., Wenzel, H.R., Tschesche, H.R., Colman, R.W. Blood (1987) [Pubmed]
  35. Binding of bovine pancreatic trypsin inhibitor to trypsinogen: spectroscopic and volumetric studies. Filfil, R., Ratavosi, A., Chalikian, T.V. Biochemistry (2004) [Pubmed]
  36. A conformational isomer of bovine pancreatic trypsin inhibitor protein produced by refolding. States, D.J., Dobson, C.M., Karplus, M., Creighton, T.E. Nature (1980) [Pubmed]
  37. A unique trypsin-like protease associated with plasma membranes of rat liver. Tanaka, K., Nakamura, T., Ichihara, A. J. Biol. Chem. (1986) [Pubmed]
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