Identification of an exosite at the neutrophil elastase/alpha-1-antitrypsin interface.

ABSTRACT: Neutrophil elastase (NE) is released by activated neutrophils during an inflammatory response and exerts proteolytic activity on elastin and other extracellular matrix components. This protease is rapidly inhibited by the plasma serine protease inhibitor alpha-1-antitrypsin (AAT), and the importance of this protective activity on lung tissue is highlighted by the development of early onset emphysema in individuals with AAT deficiency. As a serpin, AAT presents a surface-exposed reactive centre loop (RCL) whose sequence mirrors the target protease specificity. Following binding of NE in a 'Michaelis' encounter complex, cleavage of the RCL results in an irreversible complex between the two molecules. Here, the structure of the AAT-NE encounter complex was studied by molecular dynamics, mutag

SUBMITTER: Gangemi R 

PROVIDER: S-EPMC12001179 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature