5ICN
HDAC1:MTA1 in complex with inositol-6-phosphate and a novel peptide inhibitor based on histone H4
Summary for 5ICN
| Entry DOI | 10.2210/pdb5icn/pdb |
| Descriptor | Metastasis-associated protein MTA1, Histone deacetylase 1, GLY-ALA-6A0-ARG-HIS, ... (6 entities in total) |
| Functional Keywords | transcription repression inositol phosphate corepressor histone deacetylase hdac1 hdac3 histones, transcription, metastasis associated protein, ip6 |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 67157.56 |
| Authors | Millard, C.J.,Robertson, N.S.,Watson, P.J.,Jameson, A.G.,Schwabe, J.W.R. (deposition date: 2016-02-23, release date: 2016-05-11, Last modification date: 2024-10-16) |
| Primary citation | Watson, P.J.,Millard, C.J.,Riley, A.M.,Robertson, N.S.,Wright, L.C.,Godage, H.Y.,Cowley, S.M.,Jamieson, A.G.,Potter, B.V.,Schwabe, J.W. Insights into the activation mechanism of class I HDAC complexes by inositol phosphates. Nat Commun, 7:11262-11262, 2016 Cited by PubMed Abstract: 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. PubMed: 27109927DOI: 10.1038/ncomms11262 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.3 Å) |
Structure validation
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