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- Title
Structural and Biophysical Analyses of Human N-Myc Downstream-Regulated Gene 3 (NDRG3) Protein.
- Authors
Kyung Rok Kim; Kim, Kyung A.; Joon Sung Park; Jun Young Jang; Yuri Choi; Hyung Ho Lee; Dong Chul Lee; Kyung Chan Park; Young Il Yeom; Hyun-Jung Kim; Byung Woo Han
- 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.
- Subjects
AMINO acid sequence; CANCER cell migration; BIOPHYSICS; STERIC hindrance; CRYSTAL structure; CELL physiology; ASYMMETRIC dimethylarginine
- Publication
Biomolecules (2218-273X), 2020, Vol 10, Issue 1, p1
- ISSN
2218-273X
- Publication type
Article
- DOI
10.3390/biom10010090