6l4h
Crystal structure of human NDRG3 C30S mutant
Structural highlights
FunctionPublication Abstract from PubMedThe N-Myc downstream-regulated gene (NDRG) family belongs to the alpha/beta-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 A resolution, with six molecules in an asymmetric unit. While NDRG3 adopts the alpha/beta-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 alpha/beta-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 alpha6 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. Structural and Biophysical Analyses of Human N-Myc Downstream-Regulated Gene 3 (NDRG3) Protein.,Kim KR, Kim KA, Park JS, Jang JY, Choi Y, Lee HH, Lee DC, Park KC, Yeom YI, Kim HJ, Han BW Biomolecules. 2020 Jan 6;10(1). pii: biom10010090. doi: 10.3390/biom10010090. PMID:31935861[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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