Crystal structure of the human N-Myc downstream-regulated gene 2 protein provides insight into its role as a tumor suppressor |
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Authors: | Hwang Jungwon Kim Yoonjeong Kang Ho Bum Jaroszewski Lukasz Deacon Ashley M Lee Hwiseop Choi Won-Chan Kim Kyung-Jin Kim Cheol-Hee Kang Beom Sik Lee Jie-Oh Oh Tae-Kwang Kim Jae Wha Wilson Ian A Kim Myung Hee |
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Institution: | Division of Biosystems Research, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea. |
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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 α/β-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 α6 in the suppression of TCF/β-catenin signaling in the tumorigenesis of human colorectal cancer, via a molecular interaction. |
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Keywords: | Cell Differentiation Cellular Regulation Myc Tumor Suppressor X-ray Crystallography Apoptosis NDRG Family NDRG2 |
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