Studies on the role of the S4 substrate binding site of HIV proteinases

József Tözsér, Alla Gustchina, Irene T. Weber, Ivo Blaha, Ewald M. Wondrak, Stephen Oroszlan

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Kinetic analysis of the hydrolysis of the peptide H-Vat-Ser-Gin-Asn-Tyr*Pro-He-Val-Gin-NH2 and its analogs obtained by varying the length and introducing substitutions at the P4 site was carried out with both HIV-1 and HIV-2 proteinases. Deletion of the terminal Val and Gin had only moderate effect on the substrate hydrolysis, while the deletion of the P4, Ser as well as P3 Val greatly reduced the substrate hydrolysis. This is predicted to be due to the loss of interactions between main chains of the enzyme and the substrate. Substitution of the P4 Ser by amino acids having a high frequency of occurrence in β turns resulted in good substrates, while large amino acids were unfavourable in this position. The two proteinases acted similarly, except for substrates having Thr, Val and Leu substitutions, which were better accommodated in the HIV-2 substrate binding pocket.

Original languageEnglish
Pages (from-to)356-360
Number of pages5
JournalFEBS letters
Issue number2
Publication statusPublished - Feb 25 1991



  • Enzyme kinetics
  • HIV proteinase
  • Oligopeptide substrate
  • Type 1 and 2

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Tözsér, J., Gustchina, A., Weber, I. T., Blaha, I., Wondrak, E. M., & Oroszlan, S. (1991). Studies on the role of the S4 substrate binding site of HIV proteinases. FEBS letters, 279(2), 356-360.