8HAZ

Crystal structure of Caenorhabditis elegans NMAD-1 in complex with ligand I

8HAZ の概要

• エントリーDOI: 10.2210/pdb8haz/pdb
• 分子名称: DNA N6-methyl adenine demethylase, SULFATE ION (3 entities in total)
• 機能のキーワード: nmad-1a, gene regulation, oxidoreductase
• 由来する生物種: Caenorhabditis elegans
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28612.62

構造登録者

Shang, G.,Chen, Z. (登録日: 2022-10-27, 公開日: 2024-02-07)

主引用文献

Shang, G.,Yang, M.,Li, M.,Ma, L.,Liu, Y.,Ma, J.,Chen, Y.,Wang, X.,Fan, S.,Xie, M.,Wu, W.,Dai, S.,Chen, Z.
Structural Basis of Nucleic Acid Recognition and 6mA Demethylation by Caenorhabditis elegans NMAD-1A.
Int J Mol Sci, 25:-, 2024

PubMed Abstract: -methyladenine (6mA) of DNA is an emerging epigenetic mark in the genomes of , , and mammals recently. Levels of 6mA undergo drastic fluctuation and thus affect fertility during meiosis and early embryogenesis. Here, we showed three complex structures of 6mA demethylase NMAD-1A, a canonical isoform of NMAD-1 (F09F7.7). Biochemical results revealed that NMAD-1A prefers 6mA Bubble or Bulge DNAs. Structural studies of NMAD-1A revealed an unexpected "stretch-out" conformation of its Flip2 region, a conserved element that is usually bent over the catalytic center to facilitate substrate base flipping in other DNA demethylases. Moreover, the wide channel between the Flip1 and Flip2 of the NMAD-1A explained the observed preference of NMAD-1A for unpairing substrates, of which the flipped 6mA was primed for catalysis. Structural analysis and mutagenesis studies confirmed that key elements such as carboxy-terminal domain (CTD) and hypothetical zinc finger domain (ZFD) critically contributed to structural integrity, catalytic activity, and nucleosome binding. Collectively, our biochemical and structural studies suggest that NMAD-1A prefers to regulate 6mA in the unpairing regions and is thus possibly associated with dynamic chromosome regulation and meiosis regulation.

PubMed: 38255759
DOI: 10.3390/ijms25020686

実験手法

X-RAY DIFFRACTION (2.66 Å)