4BHW
Structural basis for autoinhibition of the acetyltransferase activity of p300
Summary for 4BHW
| Entry DOI | 10.2210/pdb4bhw/pdb |
| Descriptor | HISTONE ACETYLTRANSFERASE P300, ZINC ION, [(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]methyl (3R,20R)-20-carbamoyl-3-hydroxy-2,2-dimethyl-4,8,14,22-tetraoxo-12-thia-5,9,15,21-tetraazatricos-1-yl dihydrogen diphosphate, ... (4 entities in total) |
| Functional Keywords | transferase, bromodomain, phd domain, ring domain, hat domain, enhanceosome |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 2 |
| Total formula weight | 136652.84 |
| Authors | Delvecchio, M.,Gaucher, J.,Aguilar-Gurrieri, C.,Ortega, E.,Panne, D. (deposition date: 2013-04-08, release date: 2013-08-14, Last modification date: 2024-10-23) |
| Primary citation | Delvecchio, M.,Gaucher, J.,Aguilar-Gurrieri, C.,Ortega, E.,Panne, D. Structure of the P300 Catalytic Core and Implications for Chromatin Targeting and Hat Regulation Nat.Struct.Mol.Biol., 20:1040-, 2013 Cited by PubMed Abstract: CBP and p300 are histone acetyltransferases (HATs) that associate with and acetylate transcriptional regulators and chromatin. Mutations in their catalytic 'cores' are linked to genetic disorders, including cancer. Here we present the 2.8-Å crystal structure of the catalytic core of human p300 containing its bromodomain, CH2 region and HAT domain. The structure reveals that the CH2 region contains a discontinuous PHD domain interrupted by a RING domain. The bromodomain, PHD, RING and HAT domains adopt an assembled configuration with the RING domain positioned over the HAT substrate-binding pocket. Disease mutations that disrupt RING attachment led to upregulation of HAT activity, thus revealing an inhibitory role for this domain. The structure provides a starting point for understanding how chromatin-substrate targeting and HAT regulation are coupled and why mutations in the p300 core lead to dysregulation. PubMed: 23934153DOI: 10.1038/NSMB.2642 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.799 Å) |
Structure validation
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