3OPE

Structural Basis of Auto-inhibitory mechanism of Histone methyltransferase

Summary for 3OPE

• Entry DOI: 10.2210/pdb3ope/pdb
• Descriptor: Probable histone-lysine N-methyltransferase ASH1L, ZINC ION, S-ADENOSYLMETHIONINE, ... (4 entities in total)
• Functional Keywords: set, methyltransferase, nucleus, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 52561.55

Authors

An, S.,Song, J. (deposition date: 2010-08-31, release date: 2011-01-12, Last modification date: 2024-03-20)

Primary citation

An, S.,Yeo, K.J.,Jeon, Y.H.,Song, J.
Crystal structure of the human histone methyltransferase ASH1L catalytic domain and its implications for the regulatory mechanism
J.Biol.Chem., 286:8369-8374, 2011

PubMed Abstract: Absent, small, or homeotic disc1 (Ash1) is a trithorax group histone methyltransferase that is involved in gene activation. Although there are many known histone methyltransferases, their regulatory mechanisms are poorly understood. Here, we present the crystal structure of the human ASH1L catalytic domain, showing its substrate binding pocket blocked by a loop from the post-SET domain. In this configuration, the loop limits substrate access to the active site. Mutagenesis of the loop stimulates ASH1L histone methyltransferase activity, suggesting that ASH1L activity may be regulated through the loop from the post-SET domain. In addition, we show that human ASH1L specifically methylates histone H3 Lys-36. Our data implicate that there may be a regulatory mechanism of ASH1L histone methyltransferases.

PubMed: 21239497
DOI: 10.1074/jbc.M110.203380

Experimental method

X-RAY DIFFRACTION (2.9 Å)