Binding of the recombinant proteinase inhibitor eglin c from leech Hirudo medicinalis to serine (pro)enzymes: a comparative thermodynamic study
Biochemistry article published in Journal of Molecular Recognition (1991)
Abstract
The binding of the recombinant proteinase inhibitor eglin c from the leech Hirudo medicinalis to serine (pro)enzymes belonging to the chymotrypsin and subtilisin families has been investigated from the thermodynamic viewpoint, between pH 4.5 and 9.5 and from 10 degrees C to 40 degrees C. The affinity of eglin c for the serine (pro)enzymes considered shows the following trend: Leu-proteinase [the leucine specific serine proteinase from spinach (Spinacia oleracea L.) leaves] greater than human leucocyte elastase congruent to human cathepsin G congruent to subtilisin Carlsberg congruent to bovine alpha-chymotrypsin greater than bovine alpha-chymotrypsinogen A congruent to porcine pancreatic elastase congruent to bovine beta-trypsin. The serine (pro)enzyme-inhibitor complex formation is an entropy-driven process. On increasing the pH from 4.5 to 9.5, the affinity of eglin c for the serine (pro)enzymes considered increases thus reflecting the acid pK shift of the invariant hystidyl catalytic residue from approximately to 6.9 in the free serine proteinases and bovine alpha-chymotrypsinogen A to congruent to 5.1 in the serine (pro)enzyme-inhibitor complexes. Considering the known molecular models, the observed binding behaviour of eglin c was related to the inferred stereochemistry of the serine (pro)enzyme-inhibitor contact regions.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Comparative pH- and temperature-dependent thermodynamics of leech eglin C binding to multiple serine (pro)enzymes (cathepsin G, leukocyte elastase, chymotrypsin, subtilisin) reveal entropy-driven binding with affinity governed by catalytic histidine pKa shifts.
Por qué esto importa para la hirudoterapia
Este trabajo realizó una investigación termodinámica comparativa de la unión de eglin c recombinante de Hirudo medicinalis a (pro)enzimas serínicas de las familias de la quimotripsina y la subtilisina, midiendo la afinidad en un rango de pH 4,5-9,5 y 10-40 °C. La afinidad siguió la tendencia Leu-proteasa > elastasa de leucocitos humanos ≈ catepsina G humana ≈ subtilisina Carlsberg ≈ alfa-quimotripsina bovina > varios zimógenos y tripsinas, siendo la formación del complejo dirigida por entropía y aumentando la afinidad con el pH debido a un desplazamiento del pK del residuo histidilo catalítico. Para el ámbito de ASH, esto profundiza en la comprensión de cómo un inhibidor de serín-proteasa del secretoma de la sanguijuela se une a sus dianas. Advertencia: se trata de una caracterización puramente in vitro termodinámica/biofísica sin datos terapéuticos, in vivo ni de hirudoterapia.
Citación
Binding of the recombinant proteinase inhibitor eglin c from leech Hirudo medicinalis to serine (pro)enzymes: a comparative thermodynamic study.
Ascenzi P, Aducci P, Amiconi G et al. · Journal of molecular recognition, 1991
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Añadido a la biblioteca ASH: May 26, 2026 · Última actualización del sitio: 18 de junio de 2026