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Home / Equine Research Bank / Biochem J / Comparative properties of three functionally different but s...
The Biochemical journal1991; 274 ( Pt 2)(Pt 2); 465-471; doi: 10.1042/bj2740465

Comparative properties of three functionally different but structurally related serpin variants from horse plasma.

Abstract: Three structurally related but functionally different serpins from horse plasma were isolated and characterized. In spite of their identical N-terminal sequences, which show some similarity to that of human alpha 1-proteinase inhibitor, the reactive-centre loops of each of these proteins show extensive variation. Only inhibitor I, with a P1 methionine residue, resembles human alpha 1-PI with regard to (a) similarity of amino acid sequence in the vicinity of the reactive-site peptide bond, (b) broad inhibitory specificity, (c) sensitivity to oxidative inactivation and (d) high rate of reactivity with neutrophil elastase(s). Inhibitor II, with a P1 arginine residue, is an exclusive trypsin inhibitor, and inhibitor III is an oxidation-resistant slow-reacting elastase inhibitor with a P1 alanine residue. Comparison of association rate constants for the inhibition of horse neutrophil elastases by the three inhibitors indicates that only inhibitor I is likely to be physiologically important in the regulation of these enzymes.
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Publication Date: 1991-03-01 PubMed ID: 2006910PubMed Central: PMC1150162DOI: 10.1042/bj2740465Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research examines and characterizes three different but structurally related serpin variants from horse plasma. Results suggest the only serpin variant that may have significant physiological suppression on the function of horse neutrophil elastases is one that resembles the human alpha 1-proteinase inhibitor.

Characterization of Three Serpin Variants

  • The study concentrated on three serpin proteins from horse plasma which, despite having identical N-terminal sequences, exhibited major differences in their reactive-centre loops.
  • The N-terminal sequences of these serpins bear some resemblance to that of the human alpha 1-proteinase inhibitor, a protein known to inhibit the activity of proteinases, enzymes that break down proteins.

Inhibitor I Similarity to Human Alpha 1-PI

  • Inhibitor I, one of the serpin variants, demonstrated remarkable similarity with the human alpha 1-PI in multiple aspects: both share similar sequences of amino acids near the reactive-site peptide bond and both essentially inhibit a broad range of enzymes.
  • Additionally, Inhibitor I, like the human alpha 1-PI, was found to be sensitive to oxidative inactivation. That’s to say, its function may be impaired when exposed to oxygen-containing substances.
  • Both Inhibitor I and the human alpha 1-PI also showed high response rates with neutrophil elastase(s), enzymes derived from a type of white blood cells (neutrophils) involved in the breakdown of proteins.

Comparison of Inhibitor II and Inhibitor III

  • Inhibitor II, which has a P1 arginine residue, was found to be a specific inhibitor of trypsin, a protein-breaking enzyme found in the digestive system.
  • In contrast, Inhibitor III, possessing a P1 alanine residue, reflected properties of an oxidation-resistant, slow-reacting elastase inhibitor.

Physiological Importance of the Serpin Variants

  • Upon comparing the rate constants for the inhibition of horse neutrophil elastases by the three serpin variants, it was determined that only Inhibitor I is likely to significantly restrain the enzymatic activity of these elastases under physiological conditions. It indicates that Inhibitor I might have an essential physiological role in regulating these enzymes.

Cite This Article

APA
Potempa J, Wunderlich JK, Travis J. (1991). Comparative properties of three functionally different but structurally related serpin variants from horse plasma. Biochem J, 274 ( Pt 2)(Pt 2), 465-471. https://doi.org/10.1042/bj2740465

Publication

The Biochemical journal
ISSN: 0264-6021
NlmUniqueID: 2984726R
Country: England
Language: English
Volume: 274 ( Pt 2)
Issue: Pt 2
Pages: 465-471

Researcher Affiliations

Potempa, J
  • Institute of Molecular Biology, Jagiellonian University, Cracow, Poland.
Wunderlich, J K
    Travis, J

      MeSH Terms

      • Amino Acid Sequence
      • Animals
      • Endopeptidases / metabolism
      • Horses
      • Humans
      • Kinetics
      • Molecular Sequence Data
      • Sequence Homology, Nucleic Acid
      • Serpins / blood
      • Serpins / chemistry
      • Serpins / isolation & purification

      References

      This article includes 44 references
      1. Dubin A, Potempa J, Kurdowska A, Pajdak W, Koj A. Comparison of antiproteolytic activities of alpha-1-proteinase inhibitors from the plasma of some mammalian species.. Comp Biochem Physiol B 1986;83(2):375-80.
        pubmed: 3485509doi: 10.1016/0305-0491(86)90383-4google scholar: lookup
      2. Bieth JG. Pathophysiological interpretation of kinetic constants of protease inhibitors.. Bull Eur Physiopathol Respir 1980;16 Suppl:183-97.
        pubmed: 7225632doi: 10.1016/b978-0-08-027379-2.50020-xgoogle scholar: lookup
      3. Matheson NR, Gibson HL, Hallewell RA, Barr PJ, Travis J. Recombinant DNA-derived forms of human alpha 1-proteinase inhibitor. Studies on the alanine 358 and cysteine 358 substituted mutants.. J Biol Chem 1986 Aug 5;261(22):10404-9.
        pubmed: 3525544
      4. Gahne B, Juneja RK. Extensive genetic polymorphism of four plasma alpha-protease inhibitors in pigs and evidence for tight linkage between the structural loci of these inhibitors.. Anim Genet 1986;17(2):135-57.
        pubmed: 3488698doi: 10.1111/j.1365-2052.1986.tb00733.xgoogle scholar: lookup
      5. Hill RE, Shaw PH, Barth RK, Hastie ND. A genetic locus closely linked to a protease inhibitor gene complex controls the level of multiple RNA transcripts.. Mol Cell Biol 1985 Aug;5(8):2114-22.
        pubmed: 2427931doi: 10.1128/mcb.5.8.2114-2122.1985google scholar: lookup
      6. Patterson SD, Bell K. The equine protease inhibitory system (Pi): abnormal expressions of PiF, PiL, and PiS1.. Biochem Genet 1986 Aug;24(7-8):529-43.
        pubmed: 3753429doi: 10.1007/BF00504333google scholar: lookup
      7. Potempa J, Korzus E, Dubin A, Silberring J. Elastinolytic activity of horse leukocyte proteinases. Comparison with elastases from human leukocytes and porcine pancreas.. Folia Histochem Cytobiol 1986;24(2):149-56.
        pubmed: 3639830
      8. Hill RE, Hastie ND. Accelerated evolution in the reactive centre regions of serine protease inhibitors.. Nature 1987 Mar 5-11;326(6108):96-9.
        pubmed: 3493437doi: 10.1038/326096a0google scholar: lookup
      9. Yoon JB, Towle HC, Seelig S. Growth hormone induces two mRNA species of the serine protease inhibitor gene family in rat liver.. J Biol Chem 1987 Mar 25;262(9):4284-9.
        pubmed: 3494016
      10. Patterson SD, Bell K. ISO-DALT characterization of 12 'new' equine plasma protease inhibitor (Pi) alleles.. Anim Genet 1987;18(2):167-80.
        pubmed: 3662116doi: 10.1111/j.1365-2052.1987.tb00756.xgoogle scholar: lookup
      11. Boswell DR, Carrell RW. Genetic engineering and the serpins.. Bioessays 1988 Feb-Mar;8(2):83-7.
        pubmed: 3282510doi: 10.1002/bies.950080209google scholar: lookup
      12. Potempa J, Dubin A, Watorek W, Travis J. An elastase inhibitor from equine leukocyte cytosol belongs to the serpin superfamily. Further characterization and amino acid sequence of the reactive center.. J Biol Chem 1988 May 25;263(15):7364-9.
        pubmed: 3366785
      13. Carrell RW, Pemberton PA, Boswell DR. The serpins: evolution and adaptation in a family of protease inhibitors.. Cold Spring Harb Symp Quant Biol 1987;52:527-35.
        pubmed: 3502621doi: 10.1101/sqb.1987.052.01.060google scholar: lookup
      14. Padrines M, Schneider-Pozzer M, Bieth JG. Inhibition of neutrophil elastase by alpha-1-proteinase inhibitor oxidized by activated neutrophils.. Am Rev Respir Dis 1989 Mar;139(3):783-90.
        pubmed: 2784294doi: 10.1164/ajrccm/139.3.783google scholar: lookup
      15. Jallat S, Carvallo D, Tessier LH, Roecklin D, Roitsch C, Ogushi F, Crystal RG, Courtney M. Altered specificities of genetically engineered alpha 1 antitrypsin variants.. Protein Eng 1986 Oct-Nov;1(1):29-35.
        pubmed: 3509863doi: 10.1093/protein/1.1.29google scholar: lookup
      16. Patterson SD, Bell K. Application of an affinity electrophoretic and in situ oxidation method to the study of the equine protease inhibitory proteins.. Electrophoresis 1989 Jan;10(1):40-5.
        pubmed: 2714237doi: 10.1002/elps.1150100110google scholar: lookup
      17. ALEXANDER AF. Chronic alveolar emphysema in the horse.. Am Rev Respir Dis 1959 Jul;80(1, Part 2):141-6.
        pubmed: 13670415doi: 10.1164/arrd.1959.80.1P2.141google scholar: lookup
      18. Gillespie JR, Tyler WS. Chronic alveolar emphysema in the horse.. Adv Vet Sci Comp Med 1969;13:59-99.
        pubmed: 4898008
      19. Auerbach O, Hammond EC, Garfinkel L, Benante C. Relation of smoking and age to emphysema. Whole-lung section study.. N Engl J Med 1972 Apr 20;286(16):853-7.
        pubmed: 5061068doi: 10.1056/NEJM197204202861601google scholar: lookup
      20. Houmard J, Drapeau GR. Staphylococcal protease: a proteolytic enzyme specific for glutamoyl bonds.. Proc Natl Acad Sci U S A 1972 Dec;69(12):3506-9.
        pubmed: 4509307doi: 10.1073/pnas.69.12.3506google scholar: lookup
      21. Janoff A. Elastases and emphysema. Current assessment of the protease-antiprotease hypothesis.. Am Rev Respir Dis 1985 Aug;132(2):417-33.
        pubmed: 3896082doi: 10.1164/arrd.1985.132.2.417google scholar: lookup
      22. von Fellenberg R, Kohler L, Grünig G, Pellegrini A. Comparison of neutrophil elastases and of neutrophil protease inhibitors in the horse and man.. Am J Vet Res 1985 Dec;46(12):2480-4.
        pubmed: 3853453
      23. Pannell R, Johnson D, Travis J. Isolation and properties of human plasma alpha-1-proteinase inhibitor.. Biochemistry 1974 Dec 17;13(26):5439-45.
        pubmed: 4547976doi: 10.1021/bi00723a031google scholar: lookup
      24. Baugh RJ, Travis J. Human leukocyte granule elastase: rapid isolation and characterization.. Biochemistry 1976 Feb 24;15(4):836-41.
        pubmed: 1082346doi: 10.1021/bi00649a017google scholar: lookup
      25. Gadek JE, Hunninghake GW, Fells GA, Zimmerman RL, Keogh BA, Crystal RG. Evaluation of the protease-antiprotease theory of human destructive lung disease.. Bull Eur Physiopathol Respir 1980;16 Suppl:27-40.
        pubmed: 7013877doi: 10.1016/b978-0-08-027379-2.50005-3google scholar: lookup
      26. Laegreid WW, Breeze RG, Counts DF. Isolation and some properties of equine alpha 1-antitrypsin.. Int J Biochem 1982;14(4):327-34.
        pubmed: 6978269doi: 10.1016/0020-711x(82)90094-5google scholar: lookup
      27. Kurdowska A, Koj A, Jaśkowska M. Simultaneous isolation and partial characterization of antithrombin III and alpha 1-proteinase inhibitor from horse plasma.. Acta Biochim Pol 1982;29(1-2):95-103.
        pubmed: 6983800
      28. Pollitt CC, Bell K. Characterisation of the alpha 1-protease inhibitor system in Thoroughbred horse plasma by horizontal two-dimensional (ISO-DALT) electrophoresis. 2. Protease inhibition.. Anim Blood Groups Biochem Genet 1983;14(2):107-18.
        pubmed: 6604473doi: 10.1111/j.1365-2052.1983.tb01066.xgoogle scholar: lookup
      29. Pollitt CC, Bell K. Characterisation of the alpha 1-protease inhibitor system in Thoroughbred horse plasma by horizontal two-dimensional (ISO-DALT) electrophoresis. 1. Protein staining.. Anim Blood Groups Biochem Genet 1983;14(2):83-105.
        pubmed: 6193745doi: 10.1111/j.1365-2052.1983.tb01065.xgoogle scholar: lookup
      30. Travis J, Salvesen GS. Human plasma proteinase inhibitors.. Annu Rev Biochem 1983;52:655-709.
        pubmed: 6193754doi: 10.1146/annurev.bi.52.070183.003255google scholar: lookup
      31. Bell K, Patterson S, Pollitt CC. The plasma protease inhibitor system (Pi) of Standardbred horses.. Anim Blood Groups Biochem Genet 1984;15(3):191-206.
        pubmed: 6517392doi: 10.1111/j.1365-2052.1984.tb01116.xgoogle scholar: lookup
      32. Pellegrini A, Zweifel HR, von Fellenberg R. Horse alpha-1 protease inhibitors: relationship between the slow (S) and fast (F) isoforms.. Int J Biochem 1985;17(4):463-9.
        pubmed: 3891451doi: 10.1016/0020-711x(85)90141-7google scholar: lookup
      33. Dubin A, Koj A, Chudzik J. Isolation and some molecular parameters of elastase-like normal proteinases from horse blood leucocytes.. Biochem J 1976 Feb 1;153(2):389-96.
        pubmed: 6008doi: 10.1042/bj1530389google scholar: lookup
      34. Dubin A. A polyvalent proteinase inhibitor from horse-blood-leucocyte cytosol. Isolation, purification and some molecular parameters.. Eur J Biochem 1977 Mar 1;73(2):429-35.
        pubmed: 849742doi: 10.1111/j.1432-1033.1977.tb11334.xgoogle scholar: lookup
      35. Wyckoff M, Rodbard D, Chrambach A. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate-containing buffers using multiphasic buffer systems: properties of the stack, valid Rf- measurement, and optimized procedure.. Anal Biochem 1977 Apr;78(2):459-82.
        pubmed: 851219doi: 10.1016/0003-2697(77)90107-5google scholar: lookup
      36. Johnson D, Travis J. The oxidative inactivation of human alpha-1-proteinase inhibitor. Further evidence for methionine at the reactive center.. J Biol Chem 1979 May 25;254(10):4022-6.
        pubmed: 312289
      37. Carp H, Janoff A. In vitro suppression of serum elastase-inhibitory capacity by reactive oxygen species generated by phagocytosing polymorphonuclear leukocytes.. J Clin Invest 1979 Apr;63(4):793-7.
        pubmed: 220283doi: 10.1172/JCI109364google scholar: lookup
      38. McPherson EA, Lawson GH, Murphy JR, Nicholson JM, Breeze RG, Pirie HM. Chronic obstructive pulmonary disease (COPD) in horses: aetiological studies: responses to intradermal and inhalation antigenic challenge.. Equine Vet J 1979 Jul;11(3):159-66.
        pubmed: 385306doi: 10.1111/j.2042-3306.1979.tb01330.xgoogle scholar: lookup
      39. Gadek JE, Fells GA, Crystal RG. Cigarette smoking induces functional antiprotease deficiency in the lower respiratory tract of humans.. Science 1979 Dec 14;206(4424):1315-6.
        pubmed: 316188doi: 10.1126/science.316188google scholar: lookup
      40. Beatty K, Bieth J, Travis J. Kinetics of association of serine proteinases with native and oxidized alpha-1-proteinase inhibitor and alpha-1-antichymotrypsin.. J Biol Chem 1980 May 10;255(9):3931-4.
        pubmed: 6989830
      41. Juneja RK, Gahne B, Sandberg K. Genetic polymorphism and close linkage of two alpha 1-protease inhibitors in horse serum.. Anim Blood Groups Biochem Genet 1979;10(4):235-51.
        pubmed: 94978doi: 10.1111/j.1365-2052.1979.tb01031.xgoogle scholar: lookup
      42. Carp H, Janoff A. Potential mediator of inflammation. Phagocyte-derived oxidants suppress the elastase-inhibitory capacity of alpha 1-proteinase inhibitor in vitro.. J Clin Invest 1980 Nov;66(5):987-95.
        pubmed: 6253528doi: 10.1172/JCI109968google scholar: lookup
      43. Pellegrini A, von Fellenberg R. Fractionation and partial characterization of alpha-1-protease isoinhibitors of horse.. Biochim Biophys Acta 1980 Dec 4;616(2):351-61.
        pubmed: 6971123doi: 10.1016/0005-2744(80)90152-7google scholar: lookup
      44. Rabin M, Watson M, Kidd V, Woo SL, Breg WR, Ruddle FH. Regional location of alpha 1-antichymotrypsin and alpha 1-antitrypsin genes on human chromosome 14.. Somat Cell Mol Genet 1986 Mar;12(2):209-14.
        pubmed: 3485824doi: 10.1007/BF01560668google scholar: lookup

      Citations

      This article has been cited 3 times.
      1. Christensen S, Sottrup-Jensen L. Characterization of two serpins from bovine plasma and milk. Biochem J 1994 Oct 15;303 ( Pt 2)(Pt 2):383-90.
        doi: 10.1042/bj3030383pubmed: 7980396google scholar: lookup
      2. Kordula T, Dubin A, Schooltink H, Koj A, Heinrich PC, Rose-John S. Molecular cloning and expression of an intracellular serpin: an elastase inhibitor from horse leucocytes. Biochem J 1993 Jul 1;293 ( Pt 1)(Pt 1):187-93.
        doi: 10.1042/bj2930187pubmed: 7687128google scholar: lookup
      3. Patterson SD, Bell K, Shaw DC. The equine major plasma serpin multigene family: partial characterization including sequence of the reactive-site regions. Biochem Genet 1991 Oct;29(9-10):477-99.
        doi: 10.1007/BF02399689pubmed: 1772402google scholar: lookup
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