5JLE

Crystal structure of SETD2 bound to SAH

Summary for 5JLE

• Entry DOI: 10.2210/pdb5jle/pdb
• Related: 5JJY 5JLB
• Descriptor: Histone-lysine N-methyltransferase SETD2, ZINC ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• Functional Keywords: set domain, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : Q9BYW2
• Total number of polymer chains: 1
• Total formula weight: 32623.21

Authors

Li, H.,Yang, S.,Zheng, X. (deposition date: 2016-04-27, release date: 2016-11-02, Last modification date: 2023-11-08)

Primary citation

Yang, S.,Zheng, X.,Lu, C.,Li, G.M.,Allis, C.D.,Li, H.
Molecular basis for oncohistone H3 recognition by SETD2 methyltransferase
Genes Dev., 30:1611-1616, 2016

PubMed Abstract: High-frequency point mutations of genes encoding histones have been identified recently as novel drivers in a number of tumors. Specifically, the H3K36M/I mutations were shown to be oncogenic in chondroblastomas and undifferentiated sarcomas by inhibiting H3K36 methyltransferases, including SETD2. Here we report the crystal structures of the SETD2 catalytic domain bound to H3K36M or H3K36I peptides with SAH (S-adenosylhomocysteine). In the complex structure, the catalytic domain adopts an open conformation, with the K36M/I peptide snuggly positioned in a newly formed substrate channel. Our structural and biochemical data reveal the molecular basis underying oncohistone recognition by and inhibition of SETD2.

PubMed: 27474439
DOI: 10.1101/gad.284323.116

Experimental method

X-RAY DIFFRACTION (2.4 Å)