5LKU

Crystal structure of the p300 acetyltransferase catalytic core with coenzyme A.

Summary for 5LKU

• Entry DOI: 10.2210/pdb5lku/pdb
• Related: 4BHW
• Descriptor: Histone acetyltransferase p300,Histone acetyltransferase p300, ZINC ION, COENZYME A, ... (4 entities in total)
• Functional Keywords: p300 acetyltransferase, coa, chromatin modification, acylation, transferase
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm: Q09472
• Total number of polymer chains: 1
• Total formula weight: 68131.87

Authors

Kaczmarska, Z.,Ortega, E.,Marquez, J.A.,Panne, D. (deposition date: 2016-07-25, release date: 2016-11-02, Last modification date: 2024-11-06)

Primary citation

Kaczmarska, Z.,Ortega, E.,Goudarzi, A.,Huang, H.,Kim, S.,Marquez, J.A.,Zhao, Y.,Khochbin, S.,Panne, D.
Structure of p300 in complex with acyl-CoA variants.
Nat. Chem. Biol., 13:21-29, 2017

PubMed Abstract: Histone acetylation plays an important role in transcriptional activation. Histones are also modified by chemically diverse acylations that are frequently deposited by p300, a transcriptional coactivator that uses a number of different acyl-CoA cofactors. Here we report that while p300 is a robust acetylase, its activity gets weaker with increasing acyl-CoA chain length. Crystal structures of p300 in complex with propionyl-, crotonyl-, or butyryl-CoA show that the aliphatic portions of these cofactors are bound in the lysine substrate-binding tunnel in a conformation that is incompatible with substrate transfer. Lysine substrate binding is predicted to remodel the acyl-CoA ligands into a conformation compatible with acyl-chain transfer. This remodeling requires that the aliphatic portion of acyl-CoA be accommodated in a hydrophobic pocket in the enzymes active site. The size of the pocket and its aliphatic nature exclude long-chain and charged acyl-CoA variants, presumably explaining the cofactor preference for p300.

PubMed: 27820805
DOI: 10.1038/nchembio.2217

Experimental method

X-RAY DIFFRACTION (3.5 Å)