5LKX

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.52 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.208 

wwPDB Validation 3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structure of p300 in complex with acyl-CoA variants.

Kaczmarska, Z.Ortega, E.Goudarzi, A.Huang, H.Kim, S.Marquez, J.A.Zhao, Y.Khochbin, S.Panne, D.

(2017) Nat Chem Biol 13: 21-29

  • DOI: 10.1038/nchembio.2217
  • Primary Citation of Related Structures:  
    5LKU, 5LKT, 5LKX, 5LKZ

  • 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 cofac ...

    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.


    Organizational Affiliation

    European Molecular Biology Laboratory, Grenoble, France.



Macromolecules
Find similar proteins by:  (by identity cutoff)  |  Structure
Entity ID: 1
MoleculeChainsSequence LengthOrganismDetailsImage
Histone acetyltransferase p300,Histone acetyltransferase p300A578Homo sapiensMutation(s): 1 
Gene Names: EP300P300
EC: 2.3.1.48 (PDB Primary Data), 2.3.1 (UniProt)
Find proteins for Q09472 (Homo sapiens)
Explore Q09472 
Go to UniProtKB:  Q09472
NIH Common Fund Data Resources
PHAROS  Q09472
Protein Feature View
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
1VU
Query on 1VU

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A
propionyl Coenzyme A
C24 H40 N7 O17 P3 S
QAQREVBBADEHPA-IEXPHMLFSA-N
 Ligand Interaction
GOL
Query on GOL

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A
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
 Ligand Interaction
DMS
Query on DMS

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A
DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
 Ligand Interaction
ZN
Query on ZN

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A
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.52 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.208 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 93.81α = 90
b = 155.26β = 90
c = 109.79γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History 

  • Version 1.0: 2016-11-02
    Type: Initial release
  • Version 1.1: 2016-11-16
    Changes: Database references
  • Version 1.2: 2016-12-28
    Changes: Database references