2xms

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Crystal structure of human NDRG2 protein provides insight into its role as a tumor suppressor

Structural highlights

2xms is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.15Å
Ligands:CL, IMD
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NDRG2_HUMAN Contributes to the regulation of the Wnt signaling pathway. Down-regulates CTNNB1-mediated transcriptional activation of target genes, such as CCND1, and may thereby act as tumor suppressor. May be involved in dendritic cell and neuron differentiation.[1] [2] [3]

Publication Abstract from PubMed

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 alpha/beta hydrolase 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 Angstrom resolution, respectively. Both NDRG2 proteins show remarkable structural similarity to the alpha/beta hydrolase superfamily of proteins, despite limited sequence similarity. Structural analysis suggests that NDRG2 is a non-enzymatic member of the alpha/beta hydrolase superfamily, since 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 alpha6 in the suppression of TCF/beta-catenin signaling in the tumorigenesis of human colorectal cancer, via a molecular interaction.

Crystal structure of human NDRG2 protein provides insight into its role as a tumor suppressor.,Hwang J, Kim Y, Kang HB, Jaroszewski L, Deacon A, Lee H, Choi WC, Kim KJ, Kim CH, Kang BS, Lee JO, Oh TK, Kim JW, Wilson IA, Kim MH J Biol Chem. 2011 Jan 18. PMID:21247902[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
7 reviews cite this structure
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Adrain et al. (2012)
6 more
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References

  1. ↑ Deng Y, Yao L, Chau L, Ng SS, Peng Y, Liu X, Au WS, Wang J, Li F, Ji S, Han H, Nie X, Li Q, Kung HF, Leung SY, Lin MC. N-Myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation. Int J Cancer. 2003 Sep 1;106(3):342-7. PMID:12845671 doi:http://dx.doi.org/10.1002/ijc.11228
  2. ↑ Lusis EA, Watson MA, Chicoine MR, Lyman M, Roerig P, Reifenberger G, Gutmann DH, Perry A. Integrative genomic analysis identifies NDRG2 as a candidate tumor suppressor gene frequently inactivated in clinically aggressive meningioma. Cancer Res. 2005 Aug 15;65(16):7121-6. PMID:16103061 doi:http://dx.doi.org/65/16/7121
  3. ↑ Hwang J, Kim Y, Kang HB, Jaroszewski L, Deacon A, Lee H, Choi WC, Kim KJ, Kim CH, Kang BS, Lee JO, Oh TK, Kim JW, Wilson IA, Kim MH. Crystal structure of human NDRG2 protein provides insight into its role as a tumor suppressor. J Biol Chem. 2011 Jan 18. PMID:21247902 doi:10.1074/jbc.M110.170803
  4. ↑ Hwang J, Kim Y, Kang HB, Jaroszewski L, Deacon A, Lee H, Choi WC, Kim KJ, Kim CH, Kang BS, Lee JO, Oh TK, Kim JW, Wilson IA, Kim MH. Crystal structure of human NDRG2 protein provides insight into its role as a tumor suppressor. J Biol Chem. 2011 Jan 18. PMID:21247902 doi:10.1074/jbc.M110.170803

Contents


PDB ID 2xms

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