Binding of the recombinant proteinase inhibitor eglin c from leech Hirudo medicinalis to human leukocyte elastase, bovine alpha-chymotrypsin and subtilisin Carlsberg: thermodynamic study

J Enzyme Inhib. 1988;2(3):167-72. doi: 10.3109/14756368809040723.

Abstract

The effect of pH and temperature on the apparent association equilibrium constant (Ka) for the binding of the recombinant proteinase inhibitor eglin c from leech Hirudo medicinalis to human leukocyte elastase (EC 3.4.21.37), bovine alpha-chymotrypsin (EC 3.4.21.1) and subtilisin Carlsberg (EC 3.4.21.14) has been investigated. On lowering the pH from 9.5 to 4.5, values of Ka for eglin c binding to the serine proteinases considered decrease thus reflecting the acid-pK shift of the invariant histidyl catalytic residue (His57 in human leukocyte elastase and bovine alpha-chymotrypsin, and His64 in subtilisin Carlsberg) from congruent to 6.9, in the free enzymes, to congruent to 5.1, in the enzyme:inhibitor adducts. At pH 8.0, values of the apparent thermodynamic parameters for eglin c binding are: human leukocyte elastase - Ka = 1.0 x 10(10) M-1, delta G phi = -13.4 kcal/mol, delta H phi = +1.8 kcal/mol, and delta S phi = +52 entropy units; bovine alpha-chymotrypsin -Ka = 5.0 x 10(9) M-1, delta G phi = -13.0 kcal/mol, delta H phi = +2.0 kcal/mol, and delta S phi = +51 entropy units; and subtilisin Carlsberg - Ka = 6.6 x 10(9) M-1, delta G phi = -13.1 kcal/mol, delta H phi = +2.0 kcal/mol, and delta S phi = +51 entropy units (values of Ka, delta G phi and delta S phi were obtained at 21 degrees C; values of delta H phi were temperature independent over the range explored, i.e. between 10 degrees C and 40 degrees C; 1 kcal = 4184J).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Chymotrypsin / antagonists & inhibitors
  • Chymotrypsin / metabolism*
  • Humans
  • Kinetics
  • Pancreatic Elastase / antagonists & inhibitors
  • Pancreatic Elastase / metabolism*
  • Protease Inhibitors / metabolism*
  • Protein Binding
  • Proteins / metabolism*
  • Proteins / pharmacology
  • Recombinant Proteins / metabolism*
  • Recombinant Proteins / pharmacology
  • Serpins*
  • Subtilisins / antagonists & inhibitors
  • Subtilisins / metabolism*
  • Thermodynamics

Substances

  • Protease Inhibitors
  • Proteins
  • Recombinant Proteins
  • Serpins
  • eglin proteinase inhibitors
  • Subtilisins
  • Chymotrypsin
  • Pancreatic Elastase