8HB2
Crystal structure of Caenorhabditis elegans NMAD-1 in complex with ligand II
Summary for 8HB2
| Entry DOI | 10.2210/pdb8hb2/pdb |
| Descriptor | DNA N6-methyl adenine demethylase, MANGANESE (II) ION, 2-OXOGLUTARIC ACID, ... (4 entities in total) |
| Functional Keywords | nmad-1a, gene regulation, oxidoreductase |
| Biological source | Caenorhabditis elegans |
| Total number of polymer chains | 4 |
| Total formula weight | 140948.45 |
| Authors | |
| Primary citation | 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 Cited by 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: 38255759DOI: 10.3390/ijms25020686 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.06 Å) |
Structure validation
Download full validation report
