3OPE: Structural Basis Of Auto-inhibitory Mechanism Of Histone Methyltransferase

Citation:
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.
PDB ID: 3OPEDownload
MMDB ID: 87883
PDB Deposition Date: 2010/8/31
Updated in MMDB: 2011/10
Experimental Method:
x-ray diffraction
Resolution: 2.9  Å
Source Organism:
Similar Structures:
Biological Unit for 3OPE: monomeric; determined by author and by software (PISA)
Molecular Components in 3OPE
Label Count Molecule
Protein (1 molecule)
1
Probable Histone-lysine N-methyltransferase Ash1l(Gene symbol: ASH1L)
Molecule annotation
Chemicals (4 molecules)
1
3
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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