A Kazal-type inhibitor of human mast cell tryptase: isolation from the medical leech Hirudo medicinalis, characterization, and sequence analysis
Research article published in Biol Chem Hoppe Seyler (1994)
Abstract
Human tryptase, a tetrameric proteinase expressed by mast cells, is virtually unique among the serine proteinases as it is not inhibited by any proteinaceous inhibitor tested so far. We have now isolated, sequenced, and characterized an inhibitor of human tryptase from the medical leech Hirudo medicinalis. LDTI (Leech-Derived Tryptase Inhibitor) was purified to apparent homogeneity by cation exchange and affinity chromatography. Amino acid sequencing of the protein consisting of 46 residues (M(r) 4738) revealed a high degree of similarity to the non-classical Kazal-type inhibitors bdellin B-3 and rhodniin, inhibitors isolated from the medical leech and the insect Rhodnius prolixus, respectively. LDTI is a tight-binding and relatively specific inhibitor of human tryptase; it inhibits only trypsin (EC 3.4.21.4) and chymotrypsin (EC 3.4.21.1) with similar affinities. Inhibition studies using small chromogenic substrates revealed that LDTI inhibits the amidolytic activity of tryptase by approximately 50%, suggesting that most likely due to steric hindrance LDTI binds to and inhibits only 2 of 4 active sites of tryptase. LDTI appears useful as a prototype of inhibitors of human tryptase and as a pharmacological tool for the investigation of the role of tryptase in health and disease.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Leech-Derived Tryptase Inhibitor (LDTI) isolated from Hirudo medicinalis; 46-residue Kazal-type inhibitor with high similarity to bdellin B-3 and rhodniin.
Por qué esto importa para la hirudoterapia
This study reports the isolation, purification, amino acid sequencing, and functional characterization of LDTI (Leech-Derived Tryptase Inhibitor), a 46-residue protein (Mr 4738) from Hirudo medicinalis that inhibits human mast cell tryptase—a serine proteinase notably resistant to other known proteinaceous inhibitors. LDTI shows similarity to non-classical Kazal-type inhibitors (bdellin B-3, rhodniin) and also inhibits trypsin and chymotrypsin with similar affinity, binding approximately two of tryptase's four active sites to reduce amidolytic activity by ~50%. This work is relevant to ASH's domain as it identifies and characterizes a novel bioactive component of the medicinal leech secretome with potential as a pharmacological tool for studying tryptase biology. The honest caveat is that this is a biochemical characterization study with no in vivo, animal, or clinical data presented; the abstract makes no therapeutic or efficacy claims.
Citación
A Kazal-type inhibitor of human mast cell tryptase: isolation from the medical leech Hirudo medicinalis, characterization, and sequence analysis.
Sommerhoff CP et al. · Biol Chem Hoppe Seyler, 1994
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: June 18, 2026