Prostate cancer risk-associated single-nucleotide polymorphisms impact the conformational dynamics of prostate-specific antigen.

ABSTRACT:

Background

Two non-synonymous single-nucleotide polymorphisms (SNPs) rs61752561 (D95N substitution) and rs17632542 (I163T substitution) in the KLK3 gene encoding prostate-specific antigen (PSA), a chymotrypsin-like serine protease, are associated with prostate cancer risk and have been shown to reduce the activity of PSA. However, the structural impact of these SNPs on PSA, which may underlie the observed risk associations and functional alterations, has not been fully explored.

Results

Computational modelling predicted that the variants D95N and I163T do not cause drastic structural changes in PSA. However, molecular dynamics simulations suggested that while the two prominent loops of wild-type PSA remain tethered to their initial conformations over 500 ns of simulation, th

SUBMITTER: Srinivasan S 

PROVIDER: S-EPMC12821267 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature