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

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.

Resumen tomado de PubMed (NCBI) para el registro citado, en el idioma original. La versión de referencia es la de la publicación original.

El resumen se deja sin traducir para conservar la redacción original de los autores.

Purifying the isopeptidase destabilase from medicinal leech (Hirudo medicinalis) saliva, the authors sequenced two related cDNAs encoding 115- and 116-residue proteins with 14 conserved cysteines, and demonstrated isopeptidase activity from one clone.

Explore cómo esta investigación se conecta con la práctica clínica

Más estudios revisados por pares en la categoría «Desarrollo de fármacos».

• Hirudoterapia en medicina y odontología — Jha K et al. (2015)
• Terapia con sanguijuelas: una historia — Hyson J (2005)
• Hirudinas de la sanguijuela medicinal asiática Hirudinaria manillensis: iguales, pero diferentes — Lukas P et al. (2019)
• Transcriptomic analysis of the salivary gland of medicinal leech Hirudo nipponia — Lu Z et al. (2018)
• Molecular dynamic and pharmacological studies on protein-engineered hirudin variants of Hirudinaria manillensis and Hirudo medicinalis — Sun Y et al. (2022)
• Síntesis acelular de la variante 1 de hirudina de la sanguijuela hematófaga Hirudo medicinalis — Wüstenhagen D et al. (2020)
• Producción de variantes de hirudina mediante fábricas microbianas modificadas genéticamente — Zhang J, Lan N (2018)
• Hirudina en la trombocitopenia inducida por heparina — Lubenow N, Greinacher A (2002)
• La hirudina mejora la nefropatía diabética al inhibir la piroptosis mediada por Gsdmd — Han J et al. (2023)
• La hirudina como anticoagulante alternativo: una revisión histórica — Markwardt F (2002)

Ver toda la investigación analizada por la ASH →