Structural and biophysical analyses of human N-MYC downstream-regulated gene 3 (NDRG3) proteinopen access
- Authors
- 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.
- Issue Date
- Jan-2020
- Publisher
- MDPI AG
- Keywords
- Crystal structure; NDRG3; Unfolded helix; α/β-hydrolase fold
- Citation
- Biomolecules, v.10, no.1
- Journal Title
- Biomolecules
- Volume
- 10
- Number
- 1
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/38223
- DOI
- 10.3390/biom10010090
- ISSN
- 2218-273X
2218-273X
- Abstract
- 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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
- Files in This Item
-
- Appears in
Collections - Graduate School > ETC > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.