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Open AccessArticle

Structural and Biophysical Analyses of Human N-Myc Downstream-Regulated Gene 3 (NDRG3) Protein

1
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea
2
Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 08826, Korea
3
Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea
4
Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea
5
Laboratory of Molecular and Stem Cell Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 06974, Korea
*
Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(1), 90; https://doi.org/10.3390/biom10010090
Received: 18 October 2019 / Revised: 31 December 2019 / Accepted: 1 January 2020 / Published: 6 January 2020
The N-Myc downstream-regulated gene (NDRG) family belongs to the α/β-hydrolase fold and is known to exert various physiologic functions in cell proliferation, differentiation, and hypoxia-induced cancer metabolism. In particular, NDRG3 is closely related to proliferation and migration of prostate cancer cells, and recent studies reported its implication in lactate-triggered hypoxia responses or tumorigenesis. However, the underlying mechanism for the functions of NDRG3 remains unclear. Here, we report the crystal structure of human NDRG3 at 2.2 Å resolution, with six molecules in an asymmetric unit. While NDRG3 adopts the α/β-hydrolase fold, complete substitution of the canonical catalytic triad residues to non-reactive residues and steric hindrance around the pseudo-active site seem to disable the α/β-hydrolase activity. While NDRG3 shares a high similarity to NDRG2 in terms of amino acid sequence and structure, NDRG3 exhibited remarkable structural differences in a flexible loop corresponding to helix α6 of NDRG2 that is responsible for tumor suppression. Thus, this flexible loop region seems to play a distinct role in oncogenic progression induced by NDRG3. Collectively, our studies could provide structural and biophysical insights into the molecular characteristics of NDRG3. View Full-Text
Keywords: NDRG3; α/β-hydrolase fold; crystal structure; unfolded helix NDRG3; α/β-hydrolase fold; crystal structure; unfolded helix
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Kim, K.R.; Kim, K.A.; Park, J.S.; Jang, J.Y.; Choi, Y.; Lee, H.H.; Lee, D.C.; Park, K.C.; Yeom, Y.I.; Kim, H.-J.; Han, B.W. Structural and Biophysical Analyses of Human N-Myc Downstream-Regulated Gene 3 (NDRG3) Protein. Biomolecules 2020, 10, 90.

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