Crystal structure of the human N-Myc downstream-regulated gene 2 protein provides insight into its role as a tumor suppressor.

ABSTRACT: Considerable attention has recently been paid to the N-Myc downstream-regulated gene (NDRG) family because of its potential as a tumor suppressor in many human cancers. Primary amino acid sequence information suggests that the NDRG family proteins may belong to the ?/?-hydrolase (ABH) superfamily; however, their functional role has not yet been determined. Here, we present the crystal structures of the human and mouse NDRG2 proteins determined at 2.0 and 1.7 Å resolution, respectively. Both NDRG2 proteins show remarkable structural similarity to the ABH superfamily, despite limited sequence similarity. Structural analysis suggests that NDRG2 is a nonenzymatic member of the ABH superfamily, because it lacks the catalytic signature residues and has an occluded substrate-binding site. Several conserved structural features suggest NDRG may be involved in molecular interactions. Mutagenesis data based on the structural analysis support a crucial role for helix ?6 in the suppression of TCF/?-catenin signaling in the tumorigenesis of human colorectal cancer, via a molecular interaction.

SUBMITTER: Hwang J 

PROVIDER: S-EPMC3069448 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature