Novel small molecule binders of human N-glycanase 1, a key player in the endoplasmic reticulum associated degradation pathway.

ABSTRACT: Peptide:N-glycanase (NGLY1) is an enzyme responsible for cleaving oligosaccharide moieties from misfolded glycoproteins to enable their proper degradation. Deletion and truncation mutations in this gene are responsible for an inherited disorder of the endoplasmic reticulum-associated degradation pathway. However, the literature is unclear whether the disorder is a result of mutations leading to loss-of-function, loss of substrate specificity, loss of protein stability or a combination of these factors. In this communication, without burdening ourselves with the mechanistic underpinning of disease causation because of mutations on the NGLY1 protein, we demonstrate the successful application of virtual ligand screening (VLS) combined with experimental high-throughput validation to the discov

SUBMITTER: Srinivasan B 

PROVIDER: S-EPMC5015769 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature