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.
Resumen
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.
Por qué esto importa para la hirudoterapia
Este estudio termodinámico investigó la unión de eglin c recombinante —derivado de la sanguijuela Hirudo medicinalis— a la elastasa leucocitaria humana, la alfa-quimotripsina bovina y la subtilisina Carlsberg, examinando los efectos del pH y la temperatura sobre las constantes de equilibrio de asociación. La unión se caracterizó por una afinidad muy elevada (valores de Ka del orden de 10^9–10^10 M^-1) y una termodinámica favorable impulsada por la entropía, con el residuo de histidilo catalítico invariante mostrando un desplazamiento del pK ácido tras la unión del inhibidor. Para la ASH, este trabajo es relevante, ya que proporciona una caracterización fundamental a nivel molecular del mecanismo de acción de un inhibidor de proteasa del secretoma de la sanguijuela. La advertencia es que se trata de un estudio biofísico puramente in vitro, sin datos clínicos ni en animales completos, y se refiere a una proteína recombinante purificada más que a la hirudoterapia en sí misma.
Citación
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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Añadido a la biblioteca ASH: May 26, 2026 · Última actualización del sitio: 18 de junio de 2026