5LKT

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.04 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.177 

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:  

  • 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.,Université Grenoble Alpes, Institut Albert Bonniot, Grenoble, France.,Ben May Department of Cancer Research, The University of Chicago, Chicago, Illinois, USA.




Macromolecules

Find similar proteins by: Sequence  |  Structure

Entity ID: 1
MoleculeChainsSequence LengthOrganismDetails
Histone acetyltransferase p300,Histone acetyltransferase p300
A
578Homo sapiensMutation(s): 1 
Gene Names: EP300 (P300)
EC: 2.3.1.48
Find proteins for Q09472 (Homo sapiens)
Go to Gene View: EP300
Go to UniProtKB:  Q09472
Small Molecules
Ligands 5 Unique
IDChainsName / Formula / InChI Key2D Diagram3D Interactions
ZN
Query on ZN

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A
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
 Ligand Interaction
CL
Query on CL

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A
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
 Ligand Interaction
GOL
Query on GOL

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A
GLYCEROL
GLYCERIN; PROPANE-1,2,3-TRIOL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
 Ligand Interaction
BCO
Query on BCO

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A
Butyryl Coenzyme A
S-{(3S,5S,9R)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9-trihydroxy-8,8-dimethyl-3,5-dioxido-10,14-dioxo-2,4,6-trioxa-11,15-diaza-3lambda~5~,5lambda~5~-diphosphaheptadecan-17-yl} butanethioate (non-preferred name)
C25 H42 N7 O17 P3 S
CRFNGMNYKDXRTN-CITAKDKDSA-N
 Ligand Interaction
DMS
Query on DMS

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A
DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
 Ligand Interaction
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.04 Å
  • R-Value Free: 0.204 
  • R-Value Work: 0.177 
  • Space Group: C 2 2 21
Unit Cell:
Length (Å)Angle (°)
a = 92.480α = 90.00
b = 154.690β = 90.00
c = 109.230γ = 90.00
Software Package:
Software NamePurpose
XDSdata reduction
REFMACrefinement
XSCALEdata scaling
PHASERphasing

Structure Validation

View Full Validation Report or Ramachandran Plots



Entry History 

Deposition Data

Revision History 

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