PDBsum entry 2k8f

Transferase/transcription

PDB id: 2k8f

Contents

Protein chains

90 a.a. *

39 a.a. *

* Residue conservation analysis

PDB id:

2k8f

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

Date:

08-Sep-08 Release date: 03-Mar-09

Protein chain

Q09472  (EP300_HUMAN) -  Histone acetyltransferase p300 from Homo sapiens

Seq: 2414 a.a.

Struc: 90 a.a.*

Protein chain

P04637  (P53_HUMAN) -  Cellular tumor antigen p53 from Homo sapiens

Seq: 393 a.a.

Struc: 39 a.a.

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chain A: E.C.2.3.1.- - ?????
• Enzyme class 2: Chain A: E.C.2.3.1.48 - histone acetyltransferase.
• Reaction: L-lysyl-[protein] + acetyl-CoA = N₆-acetyl-L-lysyl-[protein] + CoA + H⁺
• Enzyme class 3: Chain B: E.C.?

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

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.

ABSTRACT

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.