Mechanisms of loss of functions of human angiogenin variants implicated in amyotrophic lateral sclerosis.

ABSTRACT:

Background

Mutations in the coding region of angiogenin (ANG) gene have been found in patients suffering from Amyotrophic Lateral Sclerosis (ALS). Neurodegeneration results from the loss of angiogenic ability of ANG (protein coded by ANG). In this work, we performed extensive molecular dynamics (MD) simulations of wild-type ANG and disease associated ANG variants to elucidate the mechanism behind the loss of ribonucleolytic activity and nuclear translocation activity, functions needed for angiogenesis.

Methodology/principal findings

MD simulations were carried out to study the structural and dynamic differences in the catalytic site and nuclear localization signal residues between WT-ANG (Wild-type ANG) and six mutants. Variants K17I, S28N, P112L and V113I have confirmed ass

SUBMITTER: Padhi AK 

PROVIDER: S-EPMC3288110 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature