Crystal Structure of the Human N-Myc Downstream-regulated Gene 2 Protein Provides Insight into Its Role as a Tumor Suppressor
| Autor: | Ho Bum Kang, Beom Sik Kang, Hwiseop Lee, Jungwon Hwang, Tae-Kwang Oh, Yoonjeong Kim, Cheol-Hee Kim, Myung Hee Kim, Jae Wha Kim, Won-Chan Choi, Ian A. Wilson, Jie-Oh Lee, Kyung-Jin Kim, Ashley M. Deacon, Lukasz Jaroszewski |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Structural similarity
Cellular differentiation Molecular Sequence Data Mutagenesis (molecular biology technique) Apoptosis Myc Biology Crystallography X-Ray medicine.disease_cause Biochemistry Protein Structure Secondary 03 medical and health sciences X-ray Crystallography 0302 clinical medicine Cell Line Tumor medicine Humans Immunoprecipitation Metastasis suppressor Amino Acid Sequence Molecular Biology Gene Peptide sequence 030304 developmental biology Genetics 0303 health sciences Sequence Homology Amino Acid Reverse Transcriptase Polymerase Chain Reaction Tumor Suppressor Proteins HEK 293 cells NDRG2 Cell Differentiation Cell Biology Cellular Regulation Cell biology HEK293 Cells 030220 oncology & carcinogenesis Protein Structure and Folding NDRG Family Carcinogenesis Tumor Suppressor |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m110.170803 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|