Consequences of Intramolecular Ionic Interactions for the Activation Rate of Human Pepsinogens A and C as Revealed by Molecular Modelling

  • Ruud A. Bank
  • Robert B. Russell
  • Gerard Pals
  • Michael N. G. James
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 306)


The multigene family human pepsinogen A (PGA) consists of several isozymogens.1,2 DNA sequences for PGA-3, 4, and 5 have previously been reported.3 The substitutions between the various allozymogens (PGA residue numbering according to Evers et al.) are
  1. (1)

    PGA-3: Glu43, Val77,Gln207, Ala250, Leu338;

  2. (2)

    PGA-4: Glu43, Leu77,Lys207,Thr250,Val338 and

  3. (3)

    PGA-5: Lys43, Leu77, Gln207, Ala250, Leu338.



Activation Rate Aspartic Proteinase Ionic Attraction Activation Segment Favorable Electrostatic Interaction 
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.


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  1. 1.
    R. R. Frants, J. C. Pronk, G. Pals, J. Defize, B. D. Westerveld, S. G. M. Meuwissen, J. Kreuning, A. W. Eriksson, Genetics of urinary pepsinogen: a new hypothesis, Hum. Genet., 65: 385–390 (1984).PubMedCrossRefGoogle Scholar
  2. 2.
    R. T. Taggart and I. M. Samloff, Immunochemical, electrophoretical and genetic heterogeneity of pepsinogen I. Characterization with monoclonal antibodies, Gastroenterology, 92: 143–150 (1987).PubMedGoogle Scholar
  3. 3.
    M. P. J. Evers B. Zelle, J. P. Bebelman, V. van Beusechem, L. Kraakman, M. J. V. Hoffer, J. C. Pronk, W. H. Mager, R. J. Planta, A. W. Eriksson and R. R. Frants, Nucleotide sequence comparison of five human pepsinogen A (PGA) genes: Evolution of the PGA multigene family, Genomics, 4: 232–239 (1989).PubMedCrossRefGoogle Scholar
  4. 4.
    R. A. Bank, B. C. Crusius, T. Zwiers, S. G. M. Meuwissen, F. Arwert and J. C. Pronk, Identification of a Glu → Lys substitution in the activation segment of human pepsinogen A-3 and 5 isozymogens by peptide mapping using endoproteinase Lys-C, FEBS Lett., 238: 105–108 (1988).PubMedCrossRefGoogle Scholar
  5. 5.
    B. Foltmann, Activation of human pepsinogens, FEBS Lett., 241: 69–72 (1988).PubMedCrossRefGoogle Scholar
  6. 6.
    T. Kageyama, M. Ichinose K. Miki, S. B. Athauda, M. Tanji and K. Takahashi, Difference of activation processes and structure of activation peptides in human pepsinogens A and progastricsin, J. Biochem., 105: 15–22 (1989).PubMedGoogle Scholar
  7. 7.
    S. B. P. Athauda, M. Tanji, T. Kageyama and K. Takahashi, A comparative study on the NH2-terminal amino acid sequences and some other properties of six isozymic forms of human pepsinogens and pepsins, J. Biochem., 106: 920–927 (1989).PubMedGoogle Scholar
  8. 8.
    G. Pals, T. Azuma, T. K. Mohandas, G. I. Bell, J. Bacon, I. M. Samloff, D. A. Walz, P. J. Barr and R. T. Taggart, Human pepsinogen C (progastricsin) polymorphism: evidence for a single locus located at 6p21.1-pter, Genomics, 4: 137–145 (1989).PubMedCrossRefGoogle Scholar
  9. 9.
    B. Foltmann and A. L. Jensen, Human progastricsin. Analysis of intermediates during activation into gastricsin and determination of the amino acid sequence of the propart, Eur. J. Biochem. 128: 63–70 (1982).PubMedCrossRefGoogle Scholar
  10. 10.
    M. N. G. James and A. R. Sielecki, Molecular structure of an aspartic proteinase zymogen, porcine pepsinogen at 1.8 Å resolution, Nature, 319: 33–38 (1986).PubMedCrossRefGoogle Scholar
  11. 11.
    R. A. Bank, R. B. Russell, G. Pals and M. N. G. James, Model building of human pepsinogens A and C as an aid for explaining their renal handling, Submitted for publication.Google Scholar
  12. 12.
    M. T. McCaman and D. B. Cummings, Unusual zymogen-processing properties of a mutated form of prochymosin, Proteins Struct. Funct. Genet., 3: 256–261 (1988).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Ruud A. Bank
    • 1
    • 2
  • Robert B. Russell
    • 2
  • Gerard Pals
    • 1
  • Michael N. G. James
    • 2
  1. 1.Institute of Human GeneticsFree UniversityAmsterdamThe Netherlands
  2. 2.Medical Research Council of Canada, Group in Protein Structure and Function, Department of BiochemistryUniversity of AlbertaEdmontonCanada

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