Structural Implications of Missense Point Mutations in Shwachman-Bodian-Diamond Syndrome Protein (SBDS): A Combined SAXS/MD Investigation.

ABSTRACT: Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by pleiotropic phenotypes, including pancreatic insufficiency, skeletal abnormalities, and bone marrow dysfunction. Notably, patients with SDS exhibit an increased risk of developing myelodysplastic syndrome and leukemia. In this study, we employed a combination of comparative molecular dynamics (MD) simulations and small-angle X-ray scattering (SAXS)-based analysis to investigate the Shwachman-Bodian-Diamond syndrome protein (SBDS). Specifically, we explored the molecular basis of the syndrome by examining the conformational dynamics of a set of missense mutants of SBDS in comparison to those of the wild-type (WT) protein. Our observations suggest that different mutations may impact (i) the interaction o

SUBMITTER: Mattiotti G 

PROVIDER: S-EPMC12355251 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature