Target intelligence / Profile preview

Alkaline protease 1 (Aspergillus fumigatus) (Alp1)

Target
Alp1
Molecular classification
Enzyme, Serine protease, Subtilisin family S8
01

Overview

Alkaline protease 1 (Alp1), also known as Asp f 13 or oryzin, is a major extracellular serine protease secreted by the opportunistic fungal pathogen Aspergillus fumigatus. It belongs to the subtilisin (S8) family of peptidases and serves as a critical virulence factor by degrading host proteins to facilitate fungal nutrient acquisition and tissue invasion. Alp1 has been identified as a primary mediator of airway hyperresponsiveness and inflammation in fungal-related asthma, such as severe asthma with fungal sensitization (SAFS). It acts by directly inducing the contraction of airway smooth muscle cells and degrading the extracellular matrix, which leads to structural damage in the lungs. Furthermore, Alp1 promotes immune evasion by cleaving key components of the human complement system, including C3, C4, and C5, thereby inhibiting the host's innate immune response. As a result, Alp1 is considered a promising therapeutic target for the development of novel treatments for aspergillosis and allergic fungal diseases.

Other names
Asp f 13OryzinAlkaline serine protease Alp1AFUA_4G11800
02

Mechanism of action

Inhibition of the proteolytic activity of Alp1 to prevent host tissue degradation, airway smooth muscle contraction, and immune evasion via complement cleavage.

03

Biological functions

Protein degradationImmune evasionComplement system modulationExtracellular matrix degradationInduction of airway smooth muscle contraction
04

Disease associations

Fungal asthmaInvasive aspergillosisAllergic bronchopulmonary aspergillosis (ABPA)Severe asthma with fungal sensitization (SAFS)
05

Safety considerations

Potential for off-target inhibition of host serine proteases (e.g., elastase, trypsin)Risk of incomplete fungal clearance if used as monotherapy without antifungal agents
06

Interacting drugs

Phenylmethylsulfonyl fluoride (PMSF) (experimental)

2 more in the full profile.

07

Biomarkers

Sputum Alp1 protease activitySerum IgE against Asp f 13 (Alp1)Alp1 protein levels in bronchoalveolar lavage fluid (BALF)

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