[HTML][HTML] Crystal structure of the human histone methyltransferase ASH1L catalytic domain and its implications for the regulatory mechanism
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 …
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 …