Genes from the medicinal leech Hirudo medicinalis coding for unusual enzymes that specifically cleave endo-epsilon (gamma-Glu)-Lys isopeptide bonds and help to dissolve blood clots
Research article published in Molecular & general genetics (1996)
Abstract
We previously detected in salivary gland secretions of the medicinal leech (Hirudo medicinalis) a novel enzymatic activity, endo-epsilon(gamma-Glu)-Lys isopeptidase, which cleaves isopeptide bonds formed by transglutaminase (Factor XIIIa) between glutamine gamma-carboxamide and the epsilon-amino group of lysine. Such isopeptide bonds, either within or between protein polypeptide chains are formed in many biological processes. However, before we started our work no enzymes were known to be capable of specifically splitting isopeptide bonds in proteins. The isopeptidase activity we detected was specific for isopeptide bonds. The enzyme was termed destabilase. Here we report the first purification of destabilase, part of its amino acid sequence isolation and sequencing of two related cDNAs derived from the gene family that encodes destabilase proteins, and the detection of isopeptidase activity encoded by one of these cDNAs cloned in a baculovirus expression vector. The deduced mature protein products of these cDNAs contain 115 and 116 amino acid residues, including 14 highly conserved Cys residues, and are formed from precursors containing specific leader peptides. No homologous sequences were found in public databases.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Genes from the medicinal leech Hirudo medicinalis coding for unusual enzymes that specifically cleave endo-epsilon (gamma-Glu)-Lys isopeptide bonds and help to dissolve blood clots.
Por qué esto importa para la hirudoterapia
Este estudio describe la purificación y caracterización molecular de la desestabilasa, una nueva enzima de las secreciones de las glándulas salivales de Hirudo medicinalis que escinde específicamente los enlaces isopeptídicos endo-epsilon(gama-Glu)-Lys formados por la transglutaminasa (Factor XIIIa). Los autores purificaron la enzima, determinaron la secuencia parcial de aminoácidos, aislaron dos ADNc relacionados que codifican proteínas maduras de 115 y 116 residuos con 14 residuos de Cys conservados, y confirmaron la actividad isopeptidasa a partir de un ADNc clonado en un sistema de expresión con baculovirus; no se encontraron secuencias homólogas en las bases de datos públicas. Este trabajo es directamente relevante para el ámbito de ASH, ya que caracteriza una enzima distintiva de la sanguijuela medicinal dirigida a enlaces isopeptídicos formados en procesos biológicos. No obstante, el trabajo es de naturaleza bioquímica —purificación y clonación molecular— y el resumen no informa sobre eficacia in vivo, datos clínicos ni especifica qué procesos biológicos se ven afectados.
Citación
Genes from the medicinal leech Hirudo medicinalis coding for unusual enzymes that specifically cleave endo-epsilon (gamma-Glu)-Lys isopeptide bonds and help to dissolve blood clots
Zavalova LL et al. · Molecular & general genetics, 1996
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026