Discovery of a Low Toxicity O-GlcNAc Transferase (OGT) Inhibitor by Structure-based Virtual Screening of Natural Products.

ABSTRACT: O-GlcNAc transferase (OGT) plays an important role in regulating numerous cellular processes through reversible post-translational modification of nuclear and cytoplasmic proteins. However, the function of O-GlcNAcylation is still not well understood. Cell permeable OGT inhibitors are needed to manipulate O-GlcNAcylation levels and clarify the regulatory mechanism of this modification. Here, we report a specific natural-product OGT inhibitor (L01), which was identified from a structure-based virtual screening analysis. L01 inhibited O-GlcNAcylation both in vitro and in cells without significantly altering cell surface glycans. Molecular dynamics and site-directed mutagenesis indicated a new binding mechanism in which L01 could interact with Asn557 near the UDP binding pocket of OGT. This r

SUBMITTER: Liu Y 

PROVIDER: S-EPMC5615061 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature