PDBsum entry 2k8f

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protein Protein-protein interface(s) links
Transferase/transcription PDB id
Protein chains
90 a.a. *
39 a.a. *
* Residue conservation analysis
PDB id:
Name: Transferase/transcription
Title: Structural basis for the regulation of p53 function by p300
Structure: Histone acetyltransferase p300. Chain: a. Fragment: unp residues 1723-1812. Synonym: e1a-associated protein p300. Engineered: yes. Mutation: yes. Cellular tumor antigen p53. Chain: b. Fragment: unp residues 1-39.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ep300, p300. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_variant: codonplus (de3)-ril. Gene: tp53, p53.
NMR struc: 10 models
Authors: Y.Bai,H.Feng,L.M.Jenkins,S.R.Durell,A.Wiodawer,E.Appella
Key ref:
H.Feng et al. (2009). Structural basis for p300 Taz2-p53 TAD1 binding and modulation by phosphorylation. Structure, 17, 202-210. PubMed id: 19217391 DOI: 10.1016/j.str.2008.12.009
08-Sep-08     Release date:   03-Mar-09    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q09472  (EP300_HUMAN) -  Histone acetyltransferase p300
2414 a.a.
90 a.a.*
Protein chain
Pfam   ArchSchema ?
P04637  (P53_HUMAN) -  Cellular tumor antigen p53
393 a.a.
39 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain A: E.C.  - Histone acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetyl-CoA + [histone] = CoA + acetyl-[histone]
+ [histone]
= CoA
+ acetyl-[histone]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     apoptotic process   2 terms 
  Biochemical function     transcription cofactor activity     5 terms  


    Added reference    
DOI no: 10.1016/j.str.2008.12.009 Structure 17:202-210 (2009)
PubMed id: 19217391  
Structural basis for p300 Taz2-p53 TAD1 binding and modulation by phosphorylation.
H.Feng, L.M.Jenkins, S.R.Durell, R.Hayashi, S.J.Mazur, S.Cherry, J.E.Tropea, M.Miller, A.Wlodawer, E.Appella, Y.Bai.
Coactivators CREB-binding protein and p300 play important roles in mediating the transcriptional activity of p53. Until now, however, no detailed structural information has been available on how any of the domains of p300 interact with p53. Here, we report the NMR structure of the complex of the Taz2 (C/H3) domain of p300 and the N-terminal transactivation domain of p53. In the complex, p53 forms a short alpha helix and interacts with the Taz2 domain through an extended surface. Mutational analyses demonstrate the importance of hydrophobic residues for complex stabilization. Additionally, they suggest that the increased affinity of Taz2 for p53(1-39) phosphorylated at Thr(18) is due in part to electrostatic interactions of the phosphate with neighboring arginine residues in Taz2. Thermodynamic experiments revealed the importance of hydrophobic interactions in the complex of Taz2 with p53 phosphorylated at Ser(15) and Thr(18).
  Selected figure(s)  
Figure 1.
Figure 1. Structure of the Taz2-p53[2–39] Complex
(A) Stereo image of the overlay of ten lowest-energy NMR structures of the complex between p53[15–27] (magenta) and the Taz2 domain of p300 (gray). The structures are superimposed on the Cα traces.
(B) Plot of backbone amide ^15N-{^1H} heteronuclear NOEs of p53[2–39].
(C) Cylinder model of the average conformation of the complex. p53 is shown in magenta and the helices of Taz2 are shown in blue (α1), lilac (α2), orange (α3), and red (α4). Zinc ions in Taz2, modeled as green spheres, were added according to zinc-coordination distances into the known binding cage.
(D) Secondary chemical shift difference of p53[2-39] in the complex (measured Cα chemical shift − random coil value).
Figure 2.
Figure 2. Stabilizing Interactions between p53[2–39] and Taz2
(A) Model of the Taz2-p53[2–39] complex, showing residues that make hydrophobic contacts. Contacting residues are labeled in white for Taz2 (gray surface representation) and red for p53[2–39] (blue ribbon).
(B) Model of the Taz2-p53[2–39] complex, colored by electrostatic potential (red represents negative, blue indicates positive). Taz2 is shown in a solid representation, and p53[2–39] as a mesh.
(C) Model of the Taz2-p53[2–39] complex, showing residues that make electrostatic contacts. Contacting residues are labeled in white for Taz2 (gray surface representation) and red for p53[2–39] (blue ribbon).
  The above figures are reprinted by permission from Cell Press: Structure (2009, 17, 202-210) copyright 2009.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20516128 A.C.Joerger, and A.R.Fersht (2010).
The tumor suppressor p53: from structures to drug discovery.
  Cold Spring Harb Perspect Biol, 2, a000919.  
20308326 E.Herbig, L.Warfield, L.Fish, J.Fishburn, B.A.Knutson, B.Moorefield, D.Pacheco, and S.Hahn (2010).
Mechanism of Mediator recruitment by tandem Gcn4 activation domains and three Gal11 activator-binding domains.
  Mol Cell Biol, 30, 2376-2390.  
20534573 M.L.Nelson, H.S.Kang, G.M.Lee, A.G.Blaszczak, D.K.Lau, L.P.McIntosh, and B.J.Graves (2010).
Ras signaling requires dynamic properties of Ets1 for phosphorylation-enhanced binding to coactivator CBP.
  Proc Natl Acad Sci U S A, 107, 10026-10031.
PDB code: 2kmd
20639885 M.V.Poyurovsky, C.Katz, O.Laptenko, R.Beckerman, M.Lokshin, J.Ahn, I.J.Byeon, R.Gabizon, M.Mattia, A.Zupnick, L.M.Brown, A.Friedler, and C.Prives (2010).
The C terminus of p53 binds the N-terminal domain of MDM2.
  Nat Struct Mol Biol, 17, 982-989.  
  20457558 D.W.Meek, and C.W.Anderson (2009).
Posttranslational modification of p53: cooperative integrators of function.
  Cold Spring Harb Perspect Biol, 1, a000950.  
19730431 D.W.Meek (2009).
Tumour suppression by p53: a role for the DNA damage response?
  Nat Rev Cancer, 9, 714-723.  
19966416 M.Miller, Z.Dauter, S.Cherry, J.E.Tropea, and A.Wlodawer (2009).
Structure of the Taz2 domain of p300: insights into ligand binding.
  Acta Crystallogr D Biol Crystallogr, 65, 1301-1308.
PDB code: 3io2
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.