Figure 3: Structural basis for the activation of HDAC1:MTA1 by inositol phosphates.
From: Insights into the activation mechanism of class I HDAC complexes by inositol phosphates
(a) HDAC activity of HDAC1:MTA1 is enhanced by Ins(1,4,5,6)P4, Ins(1,3,4,5,6)P5 and InsP6. A BOC-Lys-AMC assay was used - error bars indicate ±s.e.m. (n=3). (b) Crystal structure of HDAC1:MTA1 with InsP6 bound at the interface between the two proteins. The modified histone H4 peptide H4K16Hx (pink) is bound to the active site. (c,d) Three adjacent phosphates of InsP6 (purple) occupy sites A, B and C in an almost identical manner to the Ins(1,4,5,6)P4 (green) molecule bound to the HDAC3:SMRT crystal structure. However, InsP6 lies in a different orientation to Ins(1,4,5,6)P4; the ring is rotated by 120° and is tilted towards MTA1.
