3OOI

Crystal Structure of Human Histone-Lysine N-methyltransferase NSD1 SET domain in Complex with S-adenosyl-L-methionine

Summary for 3OOI

• Entry DOI: 10.2210/pdb3ooi/pdb
• Descriptor: Histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specific, ZINC ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: set domain, histone-lysine n-methyltransferase, s-adenosyl-l-methionine, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q96L73
• Total number of polymer chains: 1
• Total formula weight: 27313.03

Authors

Qiao, Q.,Wang, M.,Xu, R.M. (deposition date: 2010-08-31, release date: 2010-12-22, Last modification date: 2024-03-20)

Primary citation

Qiao, Q.,Li, Y.,Chen, Z.,Wang, M.,Reinberg, D.,Xu, R.M.
The structure of NSD1 reveals an autoregulatory mechanism underlying histone H3K36 methylation
J.Biol.Chem., 286:8361-8368, 2010

PubMed Abstract: The Sotos syndrome gene product, NSD1, is a SET domain histone methyltransferase that primarily dimethylates nucleosomal histone H3 lysine 36 (H3K36). To date, the intrinsic properties of NSD1 that determine its nucleosomal substrate selectivity and dimethyl H3K36 product specificity remain unknown. The 1.7 Å structure of the catalytic domain of NSD1 presented here shows that a regulatory loop adopts a conformation that prevents free access of H3K36 to the bound S-adenosyl-L-methionine. Molecular dynamics simulation and computational docking revealed that this normally inhibitory loop can adopt an active conformation, allowing H3K36 access to the active site, and that the nucleosome may stabilize the active conformation of the regulatory loop. Hence, our study reveals an autoregulatory mechanism of NSD1 and provides insight into the molecular mechanism of the nucleosomal substrate selectivity of this disease-related H3K36 methyltransferase.

PubMed: 21196496
DOI: 10.1074/jbc.M110.204115

Experimental method

X-RAY DIFFRACTION (1.75 Å)