Mast cell tryptase (TPS) (TPS)

Mast cell tryptase is a tetrameric serine protease stored in the secretory granules of mast cells and released into the extracellular environment upon degranulation [UniProt P23946, P20648]. It is the most abundant protein in human mast cells and serves as a key mediator of allergic and inflammatory responses [PMID: 31513869]. The enzyme exists primarily as a tetramer stabilized by heparin, which is essential for its proteolytic activity [PMID: 24985401]. Tryptase acts by cleaving various substrates, including protease-activated receptor-2 (PAR-2), which triggers the release of pro-inflammatory cytokines and promotes airway hyperresponsiveness and mucus secretion [PMID: 31513869]. In clinical practice, elevated serum tryptase levels are used as a diagnostic biomarker for mast cell activation, anaphylaxis, and systemic mastocytosis [UniProt P23946]. Therapeutically, inhibiting tryptase is pursued as a strategy to treat severe asthma, chronic obstructive pulmonary disease (COPD), and other mast cell-mediated disorders [ClinicalTrials.gov NCT03756311]. Several small molecule inhibitors and monoclonal antibodies, such as MTPS9579 and BMS-986235, have been developed to target the active site or the tetrameric structure of the enzyme [ClinicalTrials.gov NCT03756311]. However, developing potent and selective inhibitors remains a challenge due to the enzyme's unique structural requirements and the need to avoid cross-reactivity with other essential serine proteases [DrugBank DB04572].

Other names

Human tryptaseTryptase betaTryptase alphaTPSAB1TPSB2Mast cell protease II

Serine protease inhibition