Structural characterization and conformational dynamics of alpha-1 antitrypsin pathogenic variants causing alpha-1-antitrypsin deficiency.

ABSTRACT: Background: Alpha-1 antitrypsin deficiency (A1ATD) is a progressive lung disease caused by inherited pathogenic variants in the SERPINA1 gene. However, their actual role in maintenance of structural and functional characteristics of the corresponding α-1 anti-trypsin (A1AT) protein is not well characterized. Methods: The A1ATD causative SERPINA1 missense variants were initially collected from variant databases, and they were filtered based on their pathogenicity potential. Then, the tertiary protein models were constructed and the impact of individual variants on secondary structure, stability, protein-protein interactions, and molecular dynamic (MD) features of the A1AT protein was studied using diverse computational methods. Results: We identified that

SUBMITTER: Shaik NA 

PROVIDER: S-EPMC9730039 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature