Binding of the recombinant proteinase inhibitor eglin c from leech Hirudo medicinalis to human leukocyte elastase, bovine alpha-chymotrypsin and subtilisin Carlsberg: thermodynamic study
Biochemistry article published in Journal of Enzyme Inhibition (1988)
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)
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Zusammenfassung
pH- and temperature-dependent thermodynamic analysis of leech eglin c binding to human leukocyte elastase, bovine alpha-chymotrypsin, and subtilisin Carlsberg reveals entropy-driven binding with comparable Ka ~5×10^9 M⁻¹ at pH 8.
Warum dies für die Hirudotherapie relevant ist
This thermodynamic study investigated the binding of recombinant eglin c—derived from the leech Hirudo medicinalis—to human leukocyte elastase, bovine alpha-chymotrypsin, and subtilisin Carlsberg, examining the effects of pH and temperature on association equilibrium constants. Binding was characterized by very high affinity (Ka values on the order of 10^9–10^10 M^-1) and favorable entropy-driven thermodynamics, with the invariant catalytic histidyl residue showing an acid-pK shift upon inhibitor binding. For ASH, this work is relevant as it provides fundamental molecular-level characterization of a leech-secretome protease inhibitor's mechanism of action. The caveat is that this is a purely biophysical in vitro study with no clinical or whole-animal data, and it concerns a purified recombinant protein rather than hirudotherapy itself.
Zitation
Binding of the recombinant proteinase inhibitor eglin c from leech Hirudo medicinalis to human leukocyte elastase, bovine alpha-chymotrypsin and subtilisin Carlsberg: thermodynamic study.
Ascenzi P, Amiconi G, Menegatti E, Guarneri M, Bolognesi M, Schnebli HP · Journal of enzyme inhibition, 1988
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