5LKU: Crystal Structure Of The P300 Acetyltransferase Catalytic Core With Coenzyme A

Citation:
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.
PDB ID: 5LKUDownload
MMDB ID: 144583
PDB Deposition Date: 2016/7/25
Updated in MMDB: 2016/12
Experimental Method:
x-ray diffraction
Resolution: 3.5  Å
Source Organism:
Similar Structures:
Biological Unit for 5LKU: monomeric; determined by software (PISA)
Molecular Components in 5LKU
Label Count Molecule
Protein (1 molecule)
1
Histone Acetyltransferase P300,histone Acetyltransferase P300(Gene symbol: EP300)
Molecule annotation
Chemicals (5 molecules)
1
4
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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