Structural highlights
Function
MTA1_HUMAN May be involved in the regulation of gene expression by covalent modification of histone proteins. Isoform Long is a corepressor of estrogen receptor (ER). Isoform Short binds to ER and sequesters it in the cytoplasm and enhances non-genomic responses of ER.
Publication Abstract from PubMed
Histone deacetylases (HDACs) 1, 2 and 3 form the catalytic subunit of several large transcriptional repression complexes. Unexpectedly, the enzymatic activity of HDACs in these complexes has been shown to be regulated by inositol phosphates, which bind in a pocket sandwiched between the HDAC and co-repressor proteins. However, the actual mechanism of activation remains poorly understood. Here we have elucidated the stereochemical requirements for binding and activation by inositol phosphates, demonstrating that activation requires three adjacent phosphate groups and that other positions on the inositol ring can tolerate bulky substituents. We also demonstrate that there is allosteric communication between the inositol-binding site and the active site. The crystal structure of the HDAC1:MTA1 complex bound to a novel peptide-based inhibitor and to inositol hexaphosphate suggests a molecular basis of substrate recognition, and an entropically driven allosteric mechanism of activation.
Insights into the activation mechanism of class I HDAC complexes by inositol phosphates.,Watson PJ, Millard CJ, Riley AM, Robertson NS, Wright LC, Godage HY, Cowley SM, Jamieson AG, Potter BV, Schwabe JW Nat Commun. 2016 Apr 25;7:11262. doi: 10.1038/ncomms11262. PMID:27109927[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Watson PJ, Millard CJ, Riley AM, Robertson NS, Wright LC, Godage HY, Cowley SM, Jamieson AG, Potter BV, Schwabe JW. Insights into the activation mechanism of class I HDAC complexes by inositol phosphates. Nat Commun. 2016 Apr 25;7:11262. doi: 10.1038/ncomms11262. PMID:27109927 doi:http://dx.doi.org/10.1038/ncomms11262
